Next-Generation Sequencing Screening Reveals Novel Genetic Variants for Dilated Cardiomyopathy in Pediatric Chinese Patients

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Most studies focus on the genetic alterations in DCM-related genes in adult populations; however, it remains enigmatic about the mutational landscape in pediatric DCM patients, especially in the Chinese population. We exploited the next-generation sequencing (NGS) technologies to genetically analyze 46 pediatric patients and to decipher the genotype-phenotype correlation in these patients’ clinical outcomes. Our results indicated DCM-associated pathogenic mutations in 10 genes related to the structure or function of the sarcomere, desmosomal and cytoskeletal proteins. We also identified 6 pathogenic mutations (5 novel) in the titin ( TTN ) gene leading to the formation of truncated TTN protein variants in 6 (13%) out of 46 patients each. Furthermore, we investigated the correlations between TTN gene mutation and clinical outcomes in these patients. Conclusion : Our data suggest that one-third of cases of pediatric DCM are caused by genetic mutations. The role of TTN variants should not be underestimated in pediatric DCM and age-dependent pathogenic penetrance of these genetic mutations needs to be considered in the case of familial DCM. Thus, NGS analysis can be applied to decode the yet unknown DCM etiological genetic factors in pediatric as well as adult patients. Pediatrics Dilated cardiomyopathy Next-generation sequencing Pediatric patients Titin Mutation Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Dilated cardiomyopathy (DCM) is the predominant type of primitive myocardial disease, characterized by left or bilateral cardiac dilatation and systolic dysfunction in the absence of any other comorbid condition [ 1 ]. It has an estimated prevalence of 1:2500 in the general adult population, but its prevalence among children is relatively less, e.g., 1 in 170,000 in the USA and 1 in 140,000 in Australia [ 2-4 ]. Since DCM is a type of inherited heart disease, it can lead to high mortality and arrhythmias, heart failure, and sudden cardiac death [ 5 ] . About 30-50% of DCM cases are of familial origin, and sporadic DCM is more commonly observed in pediatric patients [ 6 ]. Male individuals are found to be 3 times more susceptible to DCM pathogenesis than females [ 7 , 8 ]. DCM is a genetically heterogeneous disease. Notably, children may develop familial DCM along with advanced heart failure despite the absence of such symptoms in their adult parents [ 9 , 10 ]. Previous studies have shown the association of more than 60 genes related to the structural or functional components of the cytoskeleton, desmosome, nuclear lamina, sarcomere, mitochondria, and calcium-binding proteins, with DCM pathogenesis in a Mendelian autosomal dominant pattern [ 6 , 8 , 11 , 12 ]. These genetic defects exhibit variable expressivity and variable penetrance in DCM patho-mechanism [ 13 ]. Identifying disease-causing genetic variants in probands may help asymptomatic family members to assess their risk of developing cardiomyopathy [ 14 ]. Next-generation sequencing (NGS) technology has been extensively utilized to decode the correlation between genetic mutation and phenotypic presentation in several human diseases [ 15 ]. Previous studies have primarily focused on the relationship between genetic mutation and clinical phenotype in adult DCM patients. But, the genetic landscape of pediatric DCM remains enigmatic. Therefore, in this study, we assembled a cohort of pediatric patients with DCM and presented their clinical phenotypes along with NGS analysis, including whole-exome sequencing and targeted gene panels in combination with cardiomyopathy-related gene-filtering on 46 DCM pediatric patients, identifying the underlying pathogenic mutation. For the first time, we demonstrated the linkage between genetic cause, the phenotypic presentation and clinical outcomes in pediatric patients with DCM in Shandong province in China. Furthermore, the study provides the first comprehensive landscape of genetic variation in pediatric patients with DCM by applying stringent ACMG criteria for classification, supporting genetic testing, and counseling of patients. Moreover, our investigation highlights the yet unknown clinical-pathological correlation between truncating gene mutations in titin ( TTN ) gene, a crucial component of muscle fiber, and clinical outcomes in pediatric DCM patients with Chinese genetic background. Materials And Methods Subjects and Clinical Evaluation Patients diagnosed with DCM were recruited at the pediatric department of Shandong Provincial Hospital between 2014 and 2020. Patients with specific etiologies such as congenital heart disease, myocarditis, rheumatic heart disease, systemic hypertension, cardiotoxicity, ischemic heart disease, metabolic and syndromic diseases were excluded from this study. Finally, the study cohort consisted of 46 patients (n=46; mean age 6.5 months (range: 1-156). All parents of the study subjects gave their informed consent for the study according to the Declaration of Helsinki. Echocardiographic measurements were indexed to age and body surface area (BSA), and the corresponding Z-scores were derived whenever applicable. Clinical diagnosis of DCM was performed when the Z-score of the left ventricular end-diastolic (LVEDD) and/or end-systolic volume (LVESD) was recorded above 2 standard deviations (SD) of BSA (based on Detroit data) [ 16 ], with left ventricular ejection fraction (LVEF)＜45% or fractional shortening <20% in the absence of any comorbidities [ 17 ] . Probands ≤13 years and available family members were evaluated by medical history, physical examination, 12-lead electrocardiography, and transthoracic echocardiography. We collected the clinical parameters such as age on the onset of DCM, gender, family history of DCM or sudden cardiac death, LVEF and LVEDD at the discovery set. Positive family history was defined as cardiomyopathy or sudden cardiac death (SCD) reported to clinical geneticist at the time of evaluation. Whenever possible, the positive family history was confirmed by obtaining clinical records. We set the DCM recovery parameter as LVEF≥55%. All patients were followed up in the outpatient clinic or by telephone interview until 31 st December 2020 and the mean follow-up time was 12.5 months (range: 1-84). The latest echocardiographic data and outcomes were subsequently recorded. For the survival analysis, event-free survival was calculated from the date of onset to the date of heart failure-related death. Next-Generation Sequencing and Bioinformatics Genomic DNA was extracted from peripheral blood samples using QIAamp Blood Midi Kit (QIAGEN, Germany) according to the manufacturer’s instructions. Out of 46 patients, two target panels were designed for NGS-based genetic analysis- 25 patients were analyzed by Sinopath genetic technology (Beijing, China), including 241 cardiac genes and 16 patients were analyzed by Novocardio genetic technology Co. Ltd (Beijing, China), including 101 cardiomyopathy-related genes. The remaining 5 patients’ genomic DNA was analyzed by the whole-exome sequencing (trio WES) on the Illumina platform. After filtering out low-quality reads, Burrows-Wheeler Aligner (BWA-MEM v0.7.12) was used to align the clean reads to the reference genome (UCSC Genome Browser hg19) for sorting and duplicate marking. Insertion and/or deletion (InDel) sequence determination and base quality score calibration were carried out by local realignment using Genome Analysis Toolkit software (GATK v3.2) [ 18 ]. Single-nucleotide polymorphisms (SNPs) and InDels calling were performed by GATK’s Haplotype caller [ 19 ]. All the determined variants were annotated by ANNOVAR and associated with multiple databases, such as 1000 genome, ESP6500, dbSNP, EXAC, HGMD (Human Gene Mutation Database), and were predicted by SIFT, PolyPhen-2(PP2), MutationTaster (MT), GERP++. The pathogenicities of all variants were assessed in accordance with the American College of Medical Genetics and Genomics guideline (ACMG)[ 20 ], then Sanger sequencing was performed to confirm the presence of pathogenic or likely pathogenic variants and their parental origins. Statistical analysis Statistical analysis was performed with SPSS (version 26.0) software. All data were expressed as mean ± SD or non-parametric as median and lower and upper quartiles. The difference in continuous variables was assessed by the Student’s t-test and the Mann–Whitney U test was used when the distributions were asymmetrical. Characteristics of different groups such as patients with or without disease-causing mutations were compared using the Chi-square test for categorical variables if appropriate; otherwise, Fisher’s exact test was used. The Kaplan–Meier method was used to calculate survival free from death, and the log-rank test was used to compare survival curves between different patient groups. All statistical tests were two-sided, and P values ＜ 0.05 were statistically significant. Results Clinical Characteristics The clinical characteristics of 46 (female-26 and male-20) pediatric patients with DCM onset are presented in Table 1 and Table 2. Almost all the patients were presented with a common respiratory syndrome like shortness of breath and cough. Notably, heart rhythm disturbances (1 atrial tachycardia, 2 premature ventricular contractions with low voltage, 1 transient junctional rhythm, 7 premature ventricular contractions, 2 left anterior fascicular blocks, 1 left bundle branch block, 3 atrial premature beats) were observed in 17 patients. It is important to note that 67.4% of patients (31/46) manifested the disease before 1 year of age with a median age of diagnosis of 6.5 months, and 84.8% (39/46) cases were diagnosed before the child’s third birthday. At presentation, the mean LVEF was 28.5%, and the mean LVEDD Z-score was 7.02. The mean serum N-terminal pro-brain natriuretic peptide (NT-pro BNP) level was 14406pg/ml, much higher than the reference range (Table 3). During follow-up of median 12.5 months, 54.3% of them (25/46) were recovered from DCM and their LVEF was rescued to normal range. Because of the severity of DCM, 10 out of 46 patients died, and the average death timing range was 1-36 months (median 7 months) after the initial diagnosis. Importantly, 90% of deaths occurred within the first year after diagnosis, and it was found to be a critical time period reflected by the significant morbidity and mortality. Genetic analysis of DCM showed dramatically high heterogeneity in these patients, while only 3 patients had a familial history of DCM. No significant sex difference was observed in LVEF, LVEDD Z-scores, age of onset, serum NT-proBNP level at diagnosis, and in follow-up time, the outcome of death or recovery (all P>0.05). Genetic Characteristics of Mutation-Positive Group Based on the sequencing results, the cohort was divided into two groups: the mutation-positive (MP) group (16/46) and the mutation-negative (MN) group (30/46), as shown in Table 3. Considering the stringent selection criteria and reclassification of DCM according to the ACMG guidelines, the genetic analysis suggested that these 16 patients could be classified as either ‘pathogenic’ or ‘likely pathogenic’ mutant carriers. All carriers were identified with only one pathogenic or likely pathogenic mutation in DCM-associated genes (Figure 1). We identified 10 genes with disease causing heterozygous mutations, including those with integral sarcomere functions like titin ( TTN ) [(OMIM *604145), (n=6, 37.5%)], myosin heavy chain 7 ( MYH7 ) [(OMIM *613426) (n=1, 6.25%)], troponin T2 ( TNNT2 ) [(OMIM *601494) (n=1, 6.25%)], Nexilin ( NEXN ) [(OMIM* 613122) (n=1, 6.25%)], troponin I3 ( TNNI3 ) [(OMIM*613286) (n=1, 6.25%)], cytoskeletal structure-related genes like filamin-C ( FLNC ) [(OMIM*617047) (n=1, 6.25%)], vinculin ( VCL ) [(OMIM*611407) (n=1, 6.25%)], and other genes like RNA binding motif Protein 20 ( RBM20 ) [(OMIM*613172) (n=2, 12.5%)], NK2 homeobox 5 ( NKX2-5 ) [(OMIM:108900) (n=1, 6.25%)] and PR domain containing 16 ( PRDM16 ) [(OMIM*615373) (n=1, 6.25%)]. Table 4 summarizes the main clinical features and the details of identified variants in DCM patients. Excluding 3 patients with familial mutations in TTN , MYH7 and NEXN genes, 5 de novo variants were identified in NKX2-5 , TNNI3 , PRDM16, and RBM20 (n=2) genes. Among the identified 16 gene mutations (missense-5, non-sense-5, frameshift-4 and splice site-2), 2 same mutations were identified in a pair of monozygotic (MZ) twin patients, and 10 (62.5%) other mutations were novel., In total, we identified 6 different (5 novels) TTN truncation variants, including 3 nonsense, 1 frameshift, and 2 splice-site variants, in 13% of patients (Table 4). Furthermore, we mapped the identified variants to protein domains of TTN gene (Figure 3a), which showed consistent results with previous reports. Notably, 4 variants were in I-band, and the remaining 2 in A-band and M-band regions, respectively. Genotype and Clinical Phenotype Analyses The phenotypic severity of these patients at presentation was measured by LVEDD Z-score, LVEF, and serum proBNP level. There were no significant differences in distribution based on sex (P=0.202), age (P=0.23), LVEF (P=0.935), LVEDD Z-score (P=0.42), and serum proBNP level (P=0.115) between MP and MN groups. The MP group probands exhibited lower phenotypic severity (echocardiographic parameters) than MN group DCM probands, with the same LVEF of 28.5% and LVEDD Z-score of 6.4 versus 7.08, respectively. Also, we observed a trend that the onset age (median 9.5 months) in MP group was slightly higher than that in the MN group (median 6 months). Nine MP patients developed DCM before 12 months of age, and the age distribution was between 1 month and 13 years. Despite the observation of better echocardiographic parameters and seemingly better phenotypes at presentation in MP group patients, there was no significant difference in the outcome (the number of deceased patients, P=0.145) and LVEF recovery patients, P=0.665) between the two groups during the follow-up of median time of 12.5 months (P=0.972). Survival curves free from death and recovery also showed similar results (Figure 3). 37.5% (6/16) of MP DCM patients eventually suffered from heart failure related death compared to only 13% (4/30) of the MN group. Although no significant differences in survival free of death (P= 0.093) were documented, however, there was a trend toward a worse prognosis in our patients at advanced ages (Figure 2a) when compared to the MN patients. The outcome of cardiac death occurred in patients with TTN truncating mutants (c.50065C>T, c.98421_98422insGG, c.37454-2A>T), and NKX2-5 (c.242delA), TNNT2 (c.422G>A), TNNI3 (c.544G>A) mutations. Notably, 5 out of 6 disease causing mutations belong to sarcomeric genes ( TTN =3, MYH7, TNNT2 , TNNI3 ). In this study, a significant proportion of the patients exhibited marked improvement and better prognostic outcomes in response to heart failure treatment. In both groups, almost 50% of pediatric patients could recover (LVEF above 50%). There was a trend toward better recovery in MN patients at advanced ages (Figure 2b). TTN Truncation Variants in Pediatric DCM Patients Here, we describe the clinical and genetic characteristics of 4 probands with 6 TTN mutations (as summarized in Table 4). P2 : A 12 years-old girl presented with dyspnea and fatigue. Her chest x-ray revealed enlarged heart size, and echocardiography showed LVEDD value 5.86cm and LVEF of 27%. Her brother died of severe congenital heart disease at G, p.Leu14433*) in TTN gene was confirmed in the proband and her mother by genetic analysis (Figure 4b). But her mother had no symptoms. P4 : A 12 years-old boy with DCM performed a cardiology outpatient clinical evaluation due to the sudden onset of shortened breath with abdominal pain, cough, chest tightness, and fatigue. The proband performed an electrocardiogram (ECG) showing the left anterior fascicular block. Also, he exhibited severely elevated plasmatic transaminases (AST = 275U/L, ALT = 881U/L). The abdominal CT elsewhere revealed ascites, pleural effusion. Remarkably, the plasmatic NT-proBNP level was also drastically high (960.4pg/ml) (normal values less than 125pg/ml at the proband’s age). He also performed an electrocardiogram of the left anterior fascicular block and echocardiography showing LVEF of 20%, LVEDD of 7.29cm. After receiving the regimen of spironolactone 40mg/day, captopril 8.3mg/day, furosemide 40mg/day, digoxin 0.25mg/day, potassium chloride sustained release tablets 6000mg/day for 13 days, a repeated echocardiography showed a more severe dilated left ventricle (7.45cm) and a suspicion for left ventricular apex noncompaction. Three months after diagnosis of DCM, he was hospitalized again and died of ventricular tachycardia at a young age. NGS and Sanger sequencing confirmed the ‘pathogenic’ TTN (c.50065C>T, p.Arg16689*) variant in the proband and his mother (Figure 4b). His mother had no symptoms, and she refused to perform echocardiography. For the first time, a pathogenic variant in TTN was associated with the DCM phenotype. P8: A 10 years-old girl, who suffered from DCM for about 3 years and showed no response to heart failure medication, died of heart failure and pneumonia. At the onset, she had an increased serum phosphocreatine kinase (up to 2900u/L) level, and her ECG showed premature ventricular contractions. We identified a novel ‘likely pathogenic’ frameshift mutation in TTN (c.98421_98422insGG, p.I30808Pfs * 7) by NGS analysis in the proband and her father. Her father didn’t show any symptoms. Involvement of skeletal myopathy was suspected in this patient because of increased phosphocreatine kinase level. The skeletal myopathy was then identified by muscle biopsy (failing to record the pathologic result). This suggests that this variant can cause disease in both heart and skeletal muscles. P13: A girl diagnosed with DCM at the age of 3 months had an autosomal dominant family history of DCM. Her maternal grandfather (diagnosed at 36 and died at 52 years), the brother of the grandfather (diagnosed at 42 and died at 46 years), and their sister (diagnosed at 44 and died at 52 years) died of DCM. The proband presented with shortness of breath and atrial tachycardia. She was given a treatment of dopamine cardiotonic, furosemide, spironolactone, amiodarone, and captopril. Unfortunately, 6 months later Her mother felt shortness of breath after activity and performed echocardiography elsewhere, exhibiting LVEF=29% and LVEDD=6.8cm. After 3 years of follow-up, the proband could recover her LVEF to 62% with no signs of arrhythmia. But her mother still receives drug treatment and has not been recovered yet. By trio WES method, we identified a novel truncating ‘likely pathogenic’ mutation in TTN gene (c.105541A> T, p.K35181X) in the proband and her mother, but not in her father and 8-years old brother (Figure 3), who both had normal echocardiography parameters. RBM20 Gene Mutation in Pediatric DCM P6 and P7 , monozygotic (MZ) twin brothers (a kinship coefficient of 0.4901), were diagnosed with DCM with LVEF 29% and 31%, respectively at the age of 12 years (the interval time of onset was 9 months). They both felt nausea, chest tightness, and shortness of breath. Both ECG showed ventricular premature beats. The MZ twin was administered with standard heart failure medication. After seven years of follow-up, the LVEF of the two patients were 56% and 55%, respectively, and remain asymptomatic. By WES screening, a ‘pathogenic’ de novo mutation c.2746G>A (p.E916K) in RBM20 gene was identified. The missense mutation was absent from controls (1000G, ESP, and ExAC-ALL), and was predicted to be ‘pathogenic’ by PolyPhen2, SIFT databases. The amino acid p.E916 is highly conserved across vertebrate species (Figure 5C). We confirmed this missense mutation by Sanger sequencing in the twin patients but not in their parents ( Figure 5B). Discussion DCM is a common type of pediatric heart disease leading to poor clinical outcomes and heart transplantation [ 29 , 30 ]. In this cohort, with a presentation of mean LVEF of 28.5% and the mean LVEDD Z-score of 7.02, DCM presented a severe disease phenotype. 67.4% of patients (31/46) manifested DCM before 1 year of age. Genetic factors play an important role in DCM pathogenesis. However, genetic discovery and prognostic understanding are still a challenge for DCM therapy. Hence, we sought to discover the landscape of genetic variations in pediatric patients with DCM. In this study, among 46 pediatric patients with DCM, we found that 16 (34.8%) patients carried at least one pathogenic or likely pathogenic mutation in a disease-causing gene. Consistent with previous studies, mutations in sarcomere genes were detected most frequently in all these DCM patients [ 31 ]. The prevalence of pathogenic mutations seemed to be similar as in recently published cohorts [ 32 , 33 ]. There was no difference in clinical presentations and prognosis, no matter whether there were gene mutations or not. Mutations were identified frequently in childhood-onset of DCM, especially in sarcomeric genes. Importantly, TTN -related mutations were found in 10 out of 16 MP patients. TTN truncating mutations account for 12%-27% of all adult DCM cases, suggesting the importance of diagnostic sequencing [ 34-38 ]. However, the TTN truncating mutations have been rarely identified in pediatric patients previously [ 39-41 ]. Also, recent studies in pediatric DCM have shown similar results [ 14 ]. Notably, a genetic analysis in a cohort of 66 severe childhood cardiomyopathy, including 37 DCM cases, could not identify any TTN truncating mutations in these pediatric patients [ 22 ]. Likewise, another study involving 30 Chinese pediatric subjects with sporadic DCM pathology also could not find any pathogenic TTN gene mutations [ 37 ]. However, in another study only one pathogenic TTN truncating variant has been identified in a 16 years-old boy among 36 pediatric DCM patients [ 38 ]. Obvious differently from low prevalence of TTN truncating mutants, we identified 6 different TTN truncating variants in 6 (13%) of 46 pediatric patients. The prognosis of DCM cases with TTN truncating mutations has been found to be different and conflicting in adult studies from moderate to severe outcomes. Notably, DCM patients with TTN mutations have shown a good response to treatment [ 39 ]. A cohort of 70 patients with end-stage DCM has shown recovery after left ventricle assist device implantation [ 40 ]. While another study has shown TTN mutation-positive patients frequently present severe cardiomyopathy and a worse 5-year prognosis [ 4 ]. The different clinical outcomes in TTN MP patients were also observed in our findings. Three patients with TTN mutations (c.18230-1G>A, c.43298T>G, c.105541A>T) recovered after medical treatment with no further symptom, while 3 other patients harboring TTN mutations (c.50065C>T, c.98421_98422insGG, c.37454-2A>T) showed no response to treatment and died from heart failure, suggesting clinical heterogeneity. The conflicting prognosis prompts that apart from the identified genetic factors, post-transcriptional, environmental, hormonal, and other factors could also modify the rate of disease progression. Therefore, it might be difficult to predict the clinical outcomes in pediatric DCM cases based on TTN truncating mutations alone. It has been found that the penetrance of TTN truncating mutations can reach up to 100% by the age of 70 years [ 42 ], which leads to discordant segregation with phenotype, and the same variant has also been detected in the unaffected relatives. In some pedigrees of unaffected relatives, especially in familial DCM, a clinical follow-up with aging should be carried up. The age onset of girl P13 (3 months) with TTN truncating mutation (c.105541A>T, p.K35181X) was obviously different from her mother (23 years) and her grandfather (36 years), suggesting the possible involvement of some other factors influencing DCM pathogenesis. In addition, we identified a pathogenic RBM20 variant (p.E916K) in the twin patients ( P6 and P7 ) with pediatric DCM. RBM20 mutations have been reportedly associated with cardiomyopathy [ 43 ]. Notably, the variant c.2746G>A (p.E916K) of RBM20 mutant identified in this study was located on exon11, a known hot spot for cardiomyopathy-associated mutations (Figure 6). However, the mechanistic relation of RBM20 mutations with DCM onset is still unclear. A de novo mutation in PRDM16 gene in an 8-months girl ( P9 ) was identified to be associated with pediatric DCM. Previously known mutants of this gene are mostly missense mutations; however, a nonsense mutation leading to functional loss of PRDM16 was detected in this case. The role of PRDM16 gene mutations could be very important, warranting further studies to identify its pathogenic mechanism. Limitations The study suffers from the following limitations: 1) it was a single-centered, retrospective, and a small cohort study; 2) follow-up time was not long enough to estimate the long-term outcomes; 3) clinical assessment was highly recommended for family members of the probands, but only a minority of the relatives were willing to participate in this evaluation, so gene mutation carriers of a family could be underestimated in our cohort; 4) bioinformatic prediction could give us some useful information about the pathogenicity of mutants associated with DCM, however, it cannot reflect the real pathobiology of the mutants in the cardiac myocytes. Conclusion DCM is a genetically heterogeneous disease in children and adults. Using NGS analysis, we could detect that more than one-third of cases of DCM were caused by genetic mutations in genes related to the structure or function of sarcomeric, desmosomal and cytoskeletal proteins as well as decipher their genotype-phenotype correlations in pediatric DCM patients. Here, we discovered 6 TTN truncating mutations (5 novel) correlated with severe disease phenotypes. Furthermore, we found 16 mutations in 10 genes in 16 patients that were likely to be associated with DCM pathogenesis. Most pediatric patients were diagnosed with DCM before 1 year of age. Also, most deaths occurred within the first year of life after diagnosis. The cardiac death occurred in patients harboring mutations in TTN (3), NKX2-5 (1), TNNT2 (1) genes. Hence, this study advances the genetic understanding of pediatric DCM and highlights certain genetic defects with severe clinical courses. To the best of our knowledge, this is the first study reporting that the presence of TTN truncating mutations could be associated with the onset and development of DCM in pediatric patients. Further studies are needed to define the mechanisms by which pathogenic TTN variants affect outcomes in pediatric and adult patients with DCM. Declarations Funding This study was funded by the Natural Science Foundation of China (Grant number: 81873498); Natural Science Foundation of Shandong Province (Grant number: ZR2019MH015); Jinan Science and Technology Development Plan (Grant number 201805020); and Special Expert of Taishan Scholars (Grant number: TS201511099). Conflicts of interest The authors declare that they have no conflicts of interest. Availability of data and material The data and materials are available upon request. Code availability: N/A . Authors’ Contributions All authors contributed to the study conception and design. YW and BH collected patient data and prepared the manuscript. YF, XY, JL, and JW contributed to the clinical understanding of the case and revision of the manuscript. YY, HY, LZ, and JZ analyzed and interpreted the genetic data and surveyed the literature relevant to the mutations. All authors reviewed the results and approved the final version of the manuscript. Ethics approval Our study received ethics approval (NSFC：NO.2018-115) from the ethic committee of Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University. Informed consent was obtained from all individual participants included in the study. Consent to participate : N/A. Consent for publication All authors and study participants declare their unconditional consent toward publication of this manuscript and its associated data in the peer-reviewed journal. Abbreviations ACMG, American College of Medical Genetics and Genomics. ALT, Alanine transaminase. AST, Aspartate transaminase . CT, Computed Tomography. DCM, dilated cardiomyopathy. FLNC, filamin C. HGMD, Human Gene Mutation Database. LVEDD left ventricular end-diastolic diameter. LVEF, left ventricular ejection fraction. LVNC, left ventricular noncompaction. MYH7, ß-Myosin Heavy Chain gene, MP, mutation positive. MN, mutation negative. NEXN, Nexilin F-Actin Binding Protein gene. NKX2-5, NK2 homeobox5. NGS, Next Generation Sequencing. NT-proBNP, N-terminal pro-brain-natriuretic peptide. PRDM16, positive regulatory domain16. RBM20, RNA-binding protein20. TNNI3, troponin I. TNNT2, troponin T. TTN, titin. VCL, vinculin. WES, Whole-Exome Sequencing. References Taylor MR, Carniel E, Mestroni L (2006) Cardiomyopathy, familial dilated. Orphanet J Rare Dis 1:27. https://doi.org/10.1186/1750-1172-1-27 . Puggia I, Merlo M, Barbati G, Rowland TJ, Stolfo D, Gigli M, Ramani F, et al. (2016) Natural history of dilated cardiomyopathy in children. J Am Heart Assoc 5(7). https://doi.org/10.1161/jaha.116.003450 . 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Pettersen MD, Du W, Skeens ME, Humes RA (2008) Regression equations for calculation of z scores of cardiac structures in a large cohort of healthy infants, children, and adolescents: An echocardiographic study. J Am Soc Echocardiogr 21(8):922-934. https://doi.org/10.1016/j.echo.2008.02.006 . Daubeney PE, Nugent AW, Chondros P, Carlin JB, Colan SD, Cheung M, Davis AM, et al. (2006) Clinical features and outcomes of childhood dilated cardiomyopathy: Results from a national population-based study. Circulation 114(24):2671-2678. https://doi.org/10.1161/circulationaha.106.635128 . McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, et al. (2010) The genome analysis toolkit: A mapreduce framework for analyzing next-generation DNA sequencing data. Genome Res 20(9):1297-1303. https://doi.org/10.1101/gr.107524.110 . DePristo MA, Banks E, Poplin R, Garimella KV, Maguire JR, Hartl C, Philippakis AA, et al. (2011) A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat Genet 43(5):491-498. https://doi.org/10.1038/ng.806 . Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, et al. (2015) Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the american college of medical genetics and genomics and the association for molecular pathology. Genet Med 17(5):405-424. https://doi.org/10.1038/gim.2015.30 . Miszalski-Jamka K, Jefferies JL, Mazur W, Głowacki J, Hu J, Lazar M, Gibbs RA, et al. (2017) Novel genetic triggers and genotype-phenotype correlations in patients with left ventricular noncompaction. Circ Cardiovasc Genet 10(4). https://doi.org/10.1161/circgenetics.117.001763 . Parikh VN, Caleshu C, Reuter C, Lazzeroni LC, Ingles J, Garcia J, McCaleb K, et al. (2019) Regional variation in rbm20 causes a highly penetrant arrhythmogenic cardiomyopathy. Circ Heart Fail 12(3):e005371. https://doi.org/10.1161/circheartfailure.118.005371 . Hoedemaekers YM, Cohen-Overbeek TE, Frohn-Mulder IM, Dooijes D, Majoor-Krakauer DF (2013) Prenatal ultrasound diagnosis of myh7 non-compaction cardiomyopathy. Ultrasound Obstet Gynecol 41(3):336-339. https://doi.org/10.1002/uog.12279 . Anonymous (2008) Genomics of complex disorders i. Genomic Med 2(3-4):303-330. https://doi.org/10.1007/s11568-009-9104-7 . Cuenca S, Ruiz-Cano MJ, Gimeno-Blanes JR, Jurado A, Salas C, Gomez-Diaz I, Padron-Barthe L, et al. (2016) Genetic basis of familial dilated cardiomyopathy patients undergoing heart transplantation. J Heart Lung Transplant 35(5):625-635. https://doi.org/10.1016/j.healun.2015.12.014 . Lakdawala NK, Funke BH, Baxter S, Cirino AL, Roberts AE, Judge DP, Johnson N, et al. (2012) Genetic testing for dilated cardiomyopathy in clinical practice. J Card Fail 18(4):296-303. https://doi.org/10.1016/j.cardfail.2012.01.013 . Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, Mazzarotto F, et al. (2017) Reassessment of mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. Genet Med 19(2):192-203. https://doi.org/10.1038/gim.2016.90 . Meng L, Pammi M, Saronwala A, Magoulas P, Ghazi AR, Vetrini F, Zhang J, et al. (2017) Use of exome sequencing for infants in intensive care units: Ascertainment of severe single-gene disorders and effect on medical management. JAMA Pediatr 171(12):e173438. https://doi.org/10.1001/jamapediatrics.2017.3438 . Stehlik J, Edwards LB, Kucheryavaya AY, Benden C, Christie JD, Dobbels F, Kirk R, et al. (2011) The registry of the international society for heart and lung transplantation: Twenty-eighth adult heart transplant report--2011. J Heart Lung Transplant 30(10):1078-1094. https://doi.org/10.1016/j.healun.2011.08.003 . McNally EM, Golbus JR, Puckelwartz MJ (2013) Genetic mutations and mechanisms in dilated cardiomyopathy. J Clin Invest 123(1):19-26. https://doi.org/10.1172/jci62862 . Zhao Y, Feng Y, Zhang YM, Ding XX, Song YZ, Zhang AM, Liu L, et al. (2015) Targeted next-generation sequencing of candidate genes reveals novel mutations in patients with dilated cardiomyopathy. Int J Mol Med 36(6):1479-1486. https://doi.org/10.3892/ijmm.2015.2361 . Pinto YM, Elliott PM, Arbustini E, Adler Y, Anastasakis A, Böhm M, Duboc D, et al. (2016) Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: A position statement of the esc working group on myocardial and pericardial diseases. Eur Heart J 37(23):1850-1858. https://doi.org/10.1093/eurheartj/ehv727 . Herman DS, Lam L, Taylor MR, Wang L, Teekakirikul P, Christodoulou D, Conner L, et al. (2012) Truncations of titin causing dilated cardiomyopathy. N Engl J Med 366(7):619-628. https://doi.org/10.1056/NEJMoa1110186 . Fatkin D, Huttner IG (2017) Titin-truncating mutations in dilated cardiomyopathy: The long and short of it. Curr Opin Cardiol 32(3):232-238. https://doi.org/10.1097/hco.0000000000000382 . Ellepola CD, Knight LM, Fischbach P, Deshpande SR (2018) Genetic testing in pediatric cardiomyopathy. Pediatr Cardiol 39(3):491-500. https://doi.org/10.1007/s00246-017-1779-2 . Vasilescu C, Ojala TH, Brilhante V, Ojanen S, Hinterding HM, Palin E, Alastalo TP, et al. (2018) Genetic basis of severe childhood-onset cardiomyopathies. J Am Coll Cardiol 72(19):2324-2338. https://doi.org/10.1016/j.jacc.2018.08.2171 . Dai G, Pu Z, Cheng X, Yin J, Chen J, Xu T, Zhang H, et al. (2019) Whole-exome sequencing reveals novel genetic variation for dilated cardiomyopathy in pediatric chinese patients. Pediatr Cardiol 40(5):950-957. https://doi.org/10.1007/s00246-019-02096-1 . Zaklyazminskaya E, Mikhailov V, Bukaeva A, Kotlukova N, Povolotskaya I, Kaimonov V, Dombrovskaya A, et al. (2019) Low mutation rate in the ttn gene in paediatric patients with dilated cardiomyopathy - a pilot study. Sci Rep 9(1):16409. https://doi.org/10.1038/s41598-019-52911-1 . Jansweijer JA, Nieuwhof K, Russo F, Hoorntje ET, Jongbloed JD, Lekanne Deprez RH, Postma AV, et al. (2017) Truncating titin mutations are associated with a mild and treatable form of dilated cardiomyopathy. Eur J Heart Fail 19(4):512-521. https://doi.org/10.1002/ejhf.673 . Felkin LE, Walsh R, Ware JS, Yacoub MH, Birks EJ, Barton PJ, Cook SA (2016) Recovery of cardiac function in cardiomyopathy caused by titin truncation. JAMA Cardiol 1(2):234-235. https://doi.org/10.1001/jamacardio.2016.0208 . Anderson JL, Christensen GB, Escobar H, Horne BD, Knight S, Jacobs V, Afshar K, et al. (2020) Discovery of titin gene truncating variant mutations and 5-year outcomes in patients with nonischemic dilated cardiomyopathy. Am J Cardiol 137:97-102. https://doi.org/10.1016/j.amjcard.2020.09.026 . Kayvanpour E, Sedaghat-Hamedani F, Amr A, Lai A, Haas J, Holzer DB, Frese KS, et al. (2017) Genotype-phenotype associations in dilated cardiomyopathy: Meta-analysis on more than 8000 individuals. Clin Res Cardiol 106(2):127-139. https://doi.org/10.1007/s00392-016-1033-6 . Watanabe T, Kimura A, Kuroyanagi H (2018) Alternative splicing regulator rbm20 and cardiomyopathy. Front Mol Biosci 5:105. https://doi.org/10.3389/fmolb.2018.00105 . Tables Table 1 Age Distribution of Pediatric Patients with DCM Onset. Age group years N Death (n) during follow-up females males <1 17 14 5 1-3 5 3 2 3-6 1 0 0 6-10 1 0 1 10-13 2 3 2 Total 26 20 10 Table 2 Clinical Characterization of Pediatric DCM Patients Between Female and Male Onset and Latest Outcomes. All patients, n=46 P-value Females, n=26 Males, n=20 Age, months (range) 7(1-144) 6(1-156) 0.657 LVEF% (range) 30(20-42) 27.5(17-35) 0.355 LVEDD Z-score (range) 7.46(2.36-13.65) 6.75(3.01-12.87) 0.807 NT-proBNP pg/ml (range) 15466(84.55-35000) 6485(960-35000) 0.594 Deceased during study, n (%) 6(23.1) 4(20) 0.059 Recover during study, n (%) 15(60) 10(50) 0.608 Abbreviations: LVEF, left ventricular ejection fraction; LVEDD, left ventricular end diastolic diameter (Z-score, normal reference range between -2 standard deviation [SD] and +2 SD); NT-proBNP , N-terminal fragment of pro-b-natriuretic peptide. Table 3 Clinical Characteristics of Mutation-Positive and Mutation-Negative Groups. clinical characteristics All (n=46) Mutation positive (n=16) Mutation negative (n=30) P-value Sex 0.202 Male (n%) 20(43.5) 9(56,25) 11(36.7) Female (n%) 26(56.5) 7(43.75) 19(63.3) Age onset months (range) 6.5(1-156) 9.5(1-156) 6(1.5-108) 0.23 ＜ 12 months (n%) 31(67.4) 9(56.2) 22(73.3) 12-156 months(n%) 15(32.6) 7(43.8) 8(26.7) LVEF% (range) 28.5(17-42) 28.5(20-33) 28.5(17-42) 0.935 LVEDD Z-score (range) 7.02(2.36-13.65) 6.4(3.6-13.65) 7.08(2.36-12.87) 0.42 NT-proBNP pg/ml(range) 14406(54.5-35000) 6276(960.4-35000) 16305(84.5-35000) 0.115 Follow-up (months) (range) 12.5(1-84) 12(1-84) 12.5(1-69) 0.972 Deceased during study, n (%) 10(21.7 ） 6(37.5) 4(13.3) 0.06 Recover during study, n (%) 25(54.3) 8(50) 17(56.7) 0.665 Abbreviations: LVEF, left ventricular ejection fraction; LVEDD, left ventricular end diastolic diameter (Z-score, normal reference range between -2 standard deviation [SD] and +2 SD); NT-proBNP, N-terminal pro-brain natriuretic peptide. Table 4 Clinical and Genetic Characteristics of Patients Identified in Mutation-Positive Group. Patient# Sex Age of Onset Family History Time to Death after diagnosis Modern age LVEF recovery (above50%) Arrhythmia Gene Variant (cDNA; Protein) Method Previous Reports of the Variant P1 Male 12months No - 3years Yes sinus rhythm TTN c.18230-1G>A splicing Panel 2 No P2 Female 12years No - 14years Yes premature ventricular contractions with low voltage TTN c.43298T>G p.Leu14433* Panel 2 No P3 Female 5months No - 1.9years Yes transient junctional rhythm FLNC c.4249_4250del p.Y1417*fs Panel 2 No P4 Male 12years No 3months - No left anterior fascicular block TTN c.50065C>T p.Arg16689* Panel 2 [ 21 ] P5 Male 10months No 4months - No sinus rhythm NKX2-5 c.242delA p.K81Sfs*95 Panel 1 No P6 Male 13years No - 21years Yes Low voltage, premature ventricular contractions RBM20 c.2746G>A p.E916K WES [ 22 ] P7 Male 13years No - 21years Yes Low voltage RBM20 c.2746G>A p.E916K WES [ 22 ] P8 Female 10years No 36months - No premature ventricular contractions TTN c.98421_98422insGG p.I32808Pfs*7 Panel 1 No P9 Female 8months No - 4years Yes premature ventricular contractions PRDM16 c.764C>G p.S255X Panel 1 No P10 Male 1month Brother, DCM - 7months No atrial premature beats MYH7 c.2713T>C p.C905R WES [ 23 ] P11 Female 9months No - 4years No premature ventricular contractions VCL c.142C>T p.Q48X Panel 1 No P12 Female 1.5months No 1month - No sinus rhythm TTN c.37454-2A>T splicing Panel 1 No P13 Female 3months Mother and grandfather, DCM - 4years Yes atrial tachycardia TTN c.105541A> T p.K35181X WES No P14 Male 3months Brother, heart enlarge and death - 6.5years Yes atrial premature beats NEXN c.1139_1142del p.E380Dfs*2 Panel 1 No P15 Male 18months No 1month - No sinus rhythm TNNT2 c.422G>A p.R141Q Panel 1 [ 24 , 25 ] P16 Male 3.5months No 2monthss - No premature ventricular contractions TNNI3 c.544G>A p.E182K WES [ 26-28 ] Continued Patient# Mutation type De Novo Mutation GnomAD SIFT And score MT and score PP2 and score GERP++ and score REVEL ACMG Variant Classification P1 Splicing Unknown - - D (1) - C (5.95) - Likely pathogenic PVS1; PM2 P2 Nonsense No - - A (1) - C (5.56) - Likely pathogenic PVS1; PM2 P3 Frameshift No - - - - - - Likely pathogenic PVS1; PM2 P4 Nonsense No - - A (1) - C (5.08) - pathogenic PVS1; PM3_Strong; PM2 P5 Frameshift Yes - - - - - - Likely pathogenic PVS1; PM2 P6 Missense Yes - D (0.024) N (0.849) P (0.874) C (4.71) B (0.244) Likely pathogenic PS4; PM2; BP4 P7 Missense Yes - D (0.024) N (0.849) P (0.874) C (4.71) B (0.244) Likely pathogenic PS4; PM2; BP4 P8 Frameshift No - - - - - - Likely pathogenic PVS1; PM2 P9 Nonsense Yes - - A (1) - C (3.39) - Likely pathogenic PVS1; PM2 P10 Missense No - D (0) D (1) P (0.998) C (5.55) D (0.892) Pathogenic PM3_Strong; PM1, PM2, PM5, PP3 P11 Nonsense No - - A (1) - C (4.41) - Likely pathogenic PVS1; PM2 P12 Splicing Unknown - - D (1) - C (4.34) - Likely pathogenic PVS1; PM2 P13 Nonsense No - - A (1) - C (4.78) - Likely pathogenic PVS1; PM2 P14 Frameshift No - - - - - - Likely pathogenic PVS1; PM2 P15 Missense No 0.000008 D (0) D (1) P (0.999) C (4.28) D (0.501) Likely pathogenic PS1; PM1; PP3 P16 Missense Yes - T(0.364) D (1) B (0.005) C (4.72) B (0.319) Likely pathogenic PM3_Strong, PM2, BP4 ACMG: American College of Medical Genetics and Genomics; CADD: combined annotation-dependent depletion scores; DCM: dilated cardiomyopathy; PM: pathogenic moderate; PP: pathogenic supporting; PS: pathogenic strong; BP: supporting benign; PVS: pathogenic ve ry strong; SIFT: Sorting Intolerant from Tolerant tool; WES: whole-exome sequencing; panel 1: Sinopath genetic technology including 113 cardiac genes; panel 2: Novocardio genetic technology Co. Ltd (Beijing, China), including 101 cardiomyopathy-related genes. P6 and P7 were twin brothers. SIFT Sorts intolerant from tolerant (D, damaging; T, tolerant), PP2, polymorphism phenotyping v2 (D, damaging; P, possible damaging; B, benign), MT mutation taster (D, disease causing; A, disease causing automatic; N, polymorphism; P, polymorphism_automatic) ， GERP++ genomic evolutionary rate profiling (C, conserved; N, non-conserved), Revel (D, damaging; B, benign). Supplementary Files Coverlette.docx Cite Share Download PDF Status: Published Journal Publication published 04 Aug, 2021 Read the published version in Pediatric Cardiology → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-511994","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":27300068,"identity":"a69e1d5a-3605-4c66-a313-b73a5bacac27","order_by":0,"name":"yan 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Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"hui","middleName":"","lastName":"yuan","suffix":""}],"badges":[],"createdAt":"2021-05-10 04:04:56","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-511994/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-511994/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00246-021-02698-8","type":"published","date":"2021-08-04T10:04:43+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":9260151,"identity":"431af3c6-08f4-484a-b108-7e32df2ced7b","added_by":"auto","created_at":"2021-05-17 17:18:00","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":77764,"visible":true,"origin":"","legend":"Distribution of Pathogenic or Likely Pathogenic Variants in the DCM Cohort\nIllustrates the distribution of pediatric DCM patient populations based on the mutations in genes related to either sarcomere or cytoskeletal structure or other cellular functions. Results show that 30 out of 46 patients had no underlying genetic mutation related to DCM pathogenesis. While the majority of the mutation-positive patients exhibit pathogenic or likely pathogenic mutations in the sarcomeric genes.\n","description":"","filename":"Fig.1.png","url":"https://assets-eu.researchsquare.com/files/rs-511994/v1/f25debaaf13ecb0adb3c776f.png"},{"id":9260148,"identity":"5442775d-d03a-4261-a332-bfc4ccb4e6a4","added_by":"auto","created_at":"2021-05-17 17:17:59","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":258968,"visible":true,"origin":"","legend":"Survival Curves Free from Death(a) and Recovery (EF above 50%)\na) Kaplan-Meier survival estimates of progression free from death of mutation-positive and mutation-negative DCM patients according to the genetic and clinical phenotype analyses. b) Kaplan-Meier survival estimates of progression of recovery of mutation-positive and mutation-negative groups after receiving drug treatments for heart failure and arrhythmia.\n","description":"","filename":"Fig.2.png","url":"https://assets-eu.researchsquare.com/files/rs-511994/v1/1efa892535e38be1489f15f1.png"},{"id":9260144,"identity":"3f44c611-73ad-4f43-b8ee-59f3cbe84331","added_by":"auto","created_at":"2021-05-17 17:17:57","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":292594,"visible":true,"origin":"","legend":"Illustration of Domain Mapping of TTN and Conservation of TTN Protein Amino Acid Sequences Across Vertebrates\na) Functional domains of TTN protein showing DCM-linked pathogenic or likely pathogenic mutations mostly in the I-band domain, and other mutations scattered in the A-band and M-band. b) Alignment of highly conserved TTN protein sequences for different vertebrates indicating the corresponding location of that mutation in TTN protein.\n","description":"","filename":"Fig.3.png","url":"https://assets-eu.researchsquare.com/files/rs-511994/v1/5d770d47acd3731fb45a53f5.png"},{"id":9260145,"identity":"db3f94da-6d8b-431a-a29d-c1aad9760989","added_by":"auto","created_at":"2021-05-17 17:17:58","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":237463,"visible":true,"origin":"","legend":"Pedigree Tree of 4 Patient Families harboring TTN truncating gene mutations\na) Pedigree tree of 4 families with TTN pathogenic or likely pathogenic variants for which genetic segregation was possible. All family members with available DNA samples were included. Squares indicate males, circles indicate females, slashes indicate deceased individuals, black shading indicates phenotype. The arrows indicate the proband. Heterozygous carriers (+/−) and non-carriers (−) of a TTN variant are indicated. All family members with dilated cardiomyopathy carried TTN truncating mutation. Family segregation analysis was performed in 4 families with truncating TTN mutations, and it revealed positive segregation with the disease in all cases. b) Sequencing results of the TTN mutations.\n","description":"","filename":"Fig.4.png","url":"https://assets-eu.researchsquare.com/files/rs-511994/v1/ba5b9086407d0c6168a65a91.png"},{"id":9260150,"identity":"6470a898-5038-4fe1-a0ac-ddb4e2861b4d","added_by":"auto","created_at":"2021-05-17 17:18:00","extension":"tif","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":275610,"visible":true,"origin":"","legend":"Family Pedigree of Patients P6 and P7\na) Pedigree analysis of probands P6 and P7 harboring DCM-associated RBM20 gene mutation. b) Sequence analysis of monozygotic twin probands and their parents. c) Alignment of RBM20 protein sequences across different vertebrates indicating mutation of highly conserved E916 amino acid residue.\n","description":"","filename":"Fig.5.tif","url":"https://assets-eu.researchsquare.com/files/rs-511994/v1/2911d33f01c5501dff70fa82.tif"},{"id":9260434,"identity":"d6d09ae3-4362-41d5-9c0a-3fea532108bd","added_by":"auto","created_at":"2021-05-17 17:20:59","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":101194,"visible":true,"origin":"","legend":"Mutations of RBM20 Gene in the HGMD database\nIllustration of DCM-linked mutations in RBM20 protein as documented in the Human Gene Mutation Database. The novel missense mutation p.E916K identified in our NGS analysis is indicated in red color.\n","description":"","filename":"Fig.6.png","url":"https://assets-eu.researchsquare.com/files/rs-511994/v1/9921b5eb9269781daeb7e3a9.png"},{"id":17416655,"identity":"23533a14-c99d-497f-8e9b-6d906a95a9e0","added_by":"auto","created_at":"2022-01-18 10:04:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1582584,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-511994/v1/7aebaf2f-ffe2-40a7-94da-d7d6df75dfff.pdf"},{"id":9260146,"identity":"c2d43d42-9aba-4e6e-8ad9-7a9bd279dc68","added_by":"auto","created_at":"2021-05-17 17:17:59","extension":"docx","order_by":11,"title":"","display":"","copyAsset":false,"role":"supplement","size":17689,"visible":true,"origin":"","legend":"","description":"","filename":"Coverlette.docx","url":"https://assets-eu.researchsquare.com/files/rs-511994/v1/9d7fb358a77502b722568e09.docx"}],"financialInterests":"","formattedTitle":"Next-Generation Sequencing Screening Reveals Novel Genetic Variants for Dilated Cardiomyopathy in Pediatric Chinese Patients","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDilated cardiomyopathy (DCM) is the predominant type of primitive myocardial disease, characterized by left or bilateral cardiac dilatation and systolic dysfunction in the absence of any other comorbid condition [\u003ca href=\"#_ENREF_1\"\u003e1\u003c/a\u003e]. It has an estimated prevalence of 1:2500 in the general adult population, but its prevalence among children is relatively less, e.g., 1 in 170,000 in the USA and 1 in 140,000 in Australia [\u003ca href=\"#_ENREF_2\"\u003e2-4\u003c/a\u003e]. Since DCM is a type of inherited heart disease, it can lead to high mortality and arrhythmias, heart failure, and sudden cardiac death [\u003ca href=\"#_ENREF_5\"\u003e5\u003c/a\u003e] . About 30-50% of DCM cases are of familial origin, and sporadic DCM is more commonly observed in pediatric patients [\u003ca href=\"#_ENREF_6\"\u003e6\u003c/a\u003e]. Male individuals are found to be 3 times more susceptible to DCM pathogenesis than females [\u003ca href=\"#_ENREF_7\"\u003e7\u003c/a\u003e, \u003ca href=\"#_ENREF_8\"\u003e8\u003c/a\u003e]. DCM is a genetically heterogeneous disease. Notably, children may develop familial DCM along with advanced heart failure despite the absence of such symptoms in their adult parents [\u003ca href=\"#_ENREF_9\"\u003e9\u003c/a\u003e, \u003ca href=\"#_ENREF_10\"\u003e10\u003c/a\u003e].\u003c/p\u003e\n\u003cp\u003ePrevious studies have shown the association of more than 60 genes related to the structural or functional components of the cytoskeleton, desmosome, nuclear lamina, sarcomere, mitochondria, and calcium-binding proteins, with DCM pathogenesis in a Mendelian autosomal dominant pattern [\u003ca href=\"#_ENREF_6\"\u003e6\u003c/a\u003e, \u003ca href=\"#_ENREF_8\"\u003e8\u003c/a\u003e, \u003ca href=\"#_ENREF_11\"\u003e11\u003c/a\u003e, \u003ca href=\"#_ENREF_12\"\u003e12\u003c/a\u003e]. These genetic defects exhibit variable expressivity and variable penetrance in DCM patho-mechanism [\u003ca href=\"#_ENREF_13\"\u003e13\u003c/a\u003e]. Identifying disease-causing genetic variants in probands may help asymptomatic family members to assess their risk of developing cardiomyopathy [\u003ca href=\"#_ENREF_14\"\u003e14\u003c/a\u003e]. Next-generation sequencing (NGS) technology has been extensively utilized to decode the correlation between genetic mutation and phenotypic presentation in several human diseases [\u003ca href=\"#_ENREF_15\"\u003e15\u003c/a\u003e]. Previous studies have primarily focused on the relationship between genetic mutation and clinical phenotype in adult DCM patients. But, the genetic landscape of pediatric DCM remains enigmatic. Therefore, in this study, we assembled a cohort of pediatric patients with DCM and presented their clinical phenotypes along with NGS analysis, including whole-exome sequencing and targeted\u0026nbsp;gene\u0026nbsp;panels in combination with cardiomyopathy-related gene-filtering on 46 DCM pediatric patients, identifying the underlying pathogenic mutation. For the first time, we demonstrated the linkage between genetic cause, the phenotypic presentation and clinical outcomes in pediatric patients with DCM in Shandong province in China. Furthermore, the study provides the first comprehensive landscape of genetic variation in pediatric patients with DCM by applying stringent ACMG criteria for classification, supporting genetic testing, and counseling of patients. Moreover, our investigation highlights the yet unknown clinical-pathological correlation between truncating gene mutations in titin (\u003cem\u003eTTN\u003c/em\u003e) gene, a crucial component of muscle fiber, and clinical outcomes in pediatric DCM patients with Chinese genetic background.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cp\u003e\u003cstrong\u003eSubjects and Clinical Evaluation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients diagnosed with DCM were recruited at the pediatric department of Shandong Provincial Hospital between 2014 and 2020. Patients with specific etiologies such as congenital heart disease, myocarditis, rheumatic heart disease, systemic hypertension, cardiotoxicity, ischemic heart disease, metabolic and syndromic diseases were excluded from this study. Finally, the study cohort consisted of 46 patients (n=46; mean age 6.5 months (range: 1-156). All parents of the study subjects gave their informed consent for the study according to the Declaration of Helsinki. Echocardiographic measurements were indexed to age and body surface area (BSA), and the corresponding Z-scores were derived whenever applicable. Clinical diagnosis of DCM was performed when the Z-score of the left ventricular end-diastolic (LVEDD) and/or end-systolic volume (LVESD) was recorded above 2 standard deviations (SD) of BSA (based on Detroit data) [\u003ca href=\"#_ENREF_16\"\u003e16\u003c/a\u003e], with left ventricular ejection fraction (LVEF)＜45% or fractional shortening \u0026lt;20% in the absence of any comorbidities [\u003ca href=\"#_ENREF_17\"\u003e17\u003c/a\u003e]\u003cstrong\u003e. \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eProbands \u0026le;13 years and available family members were evaluated by medical history, physical examination, 12-lead electrocardiography, and transthoracic echocardiography. We collected the clinical parameters such as age on the onset of DCM, gender, family history of DCM or sudden cardiac death, LVEF and LVEDD at the discovery set. Positive family history was defined as cardiomyopathy or sudden cardiac death (SCD) reported to clinical geneticist at the time of evaluation. Whenever possible, the positive family history was confirmed by obtaining clinical records. We set the DCM recovery parameter as LVEF\u0026ge;55%. \u0026nbsp;All\u0026nbsp;patients\u0026nbsp;were\u0026nbsp;followed up\u0026nbsp;in\u0026nbsp;the\u0026nbsp;outpatient clinic or by telephone interview until 31\u003csup\u003est\u003c/sup\u003e December 2020 and\u0026nbsp;the\u0026nbsp;mean follow-up\u0026nbsp;time was 12.5 months (range: 1-84). The latest echocardiographic data and outcomes were subsequently recorded. For the survival analysis, event-free survival was calculated from the date of onset to the date of heart failure-related death.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNext-Generation Sequencing\u003c/strong\u003e\u003cstrong\u003e and Bioinformatics \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGenomic DNA was extracted from peripheral blood samples using QIAamp Blood Midi Kit (QIAGEN, Germany) according to the manufacturer\u0026rsquo;s instructions. Out of 46 patients, two target panels were designed for NGS-based genetic analysis- 25 patients were analyzed by Sinopath genetic technology (Beijing, China), including 241 cardiac genes and 16 patients were analyzed by Novocardio genetic technology Co. Ltd (Beijing, China), including 101 cardiomyopathy-related genes. The remaining 5 patients\u0026rsquo; genomic DNA was analyzed by the whole-exome sequencing (trio WES) on the Illumina platform.\u003c/p\u003e\n\u003cp\u003eAfter filtering out low-quality reads, Burrows-Wheeler Aligner (BWA-MEM v0.7.12) was used to align the clean reads to the reference genome (UCSC Genome Browser hg19) for sorting and duplicate marking. Insertion and/or deletion (InDel) sequence determination and base quality score calibration were carried out by local realignment using Genome Analysis Toolkit software (GATK v3.2) [\u003ca href=\"#_ENREF_18\"\u003e18\u003c/a\u003e]. Single-nucleotide polymorphisms (SNPs) and InDels calling were performed by GATK\u0026rsquo;s Haplotype caller [\u003ca href=\"#_ENREF_19\"\u003e19\u003c/a\u003e]. All the determined variants were annotated by ANNOVAR and associated with multiple databases, such as 1000 genome, ESP6500, dbSNP, EXAC, HGMD (Human Gene Mutation Database), and were predicted by SIFT, PolyPhen-2(PP2), MutationTaster (MT), GERP++.\u003c/p\u003e\n\u003cp\u003eThe pathogenicities of all variants were assessed in accordance with the American College of Medical Genetics and Genomics guideline (ACMG)[\u003ca href=\"#_ENREF_20\"\u003e20\u003c/a\u003e], then Sanger sequencing was performed to confirm the presence of pathogenic or likely pathogenic variants and their parental origins.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analysis was performed with SPSS (version 26.0) software. All data were expressed as mean \u0026plusmn; SD or non-parametric as median and lower and upper quartiles. The difference in continuous variables was assessed by the Student\u0026rsquo;s t-test and the Mann\u0026ndash;Whitney U test was used when the distributions were asymmetrical. Characteristics of different groups such as patients with or without disease-causing mutations were compared using the Chi-square test for categorical variables if appropriate; otherwise, Fisher\u0026rsquo;s exact test was used. The Kaplan\u0026ndash;Meier method was used to calculate survival free from death, and the log-rank test was used to compare survival curves between different patient groups. All statistical tests were two-sided, and P values ＜ 0.05 were statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eClinical Characteristics \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe clinical characteristics of 46 (female-26 and male-20) pediatric patients with DCM onset are presented in Table 1 and Table 2. Almost all the patients were presented with a common respiratory syndrome like shortness of\u0026nbsp;breath\u0026nbsp;and\u0026nbsp;cough. Notably, heart rhythm disturbances (1 atrial\u0026nbsp;tachycardia, 2 premature\u0026nbsp;ventricular\u0026nbsp;contractions with low\u0026nbsp;voltage, 1 transient\u0026nbsp;junctional\u0026nbsp;rhythm, 7 premature\u0026nbsp;ventricular\u0026nbsp;contractions, 2 left\u0026nbsp;anterior\u0026nbsp;fascicular\u0026nbsp;blocks, 1 left\u0026nbsp;bundle\u0026nbsp;branch\u0026nbsp;block, 3 atrial\u0026nbsp;premature\u0026nbsp;beats) were observed in 17 patients. It\u0026nbsp;is\u0026nbsp;important to note\u0026nbsp;that 67.4% of patients (31/46) manifested the disease before 1 year of age with a median age of diagnosis of 6.5 months, and 84.8% (39/46) cases were diagnosed before the child\u0026rsquo;s third birthday. At presentation, the mean LVEF was 28.5%, and the mean LVEDD Z-score was 7.02. The mean serum N-terminal pro-brain natriuretic peptide (NT-pro BNP) level was 14406pg/ml, much higher than the reference range (Table 3). During follow-up of median 12.5 months, 54.3% of them (25/46) were recovered from DCM and their LVEF was rescued to normal range. Because of the severity of DCM, 10 out of 46 patients died, and the average death timing range was 1-36 months (median 7 months) after the initial diagnosis. Importantly, 90% of deaths occurred within the first year after diagnosis, and it was found to be a critical time period reflected by the significant morbidity and mortality.\u0026nbsp;Genetic analysis of DCM showed dramatically high heterogeneity in these patients, while only 3 patients had a familial history of DCM. No significant sex difference was observed in LVEF, LVEDD Z-scores, age of onset, serum NT-proBNP level at diagnosis, and in follow-up time, the outcome of death or recovery (all P\u0026gt;0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGenetic Characteristics of Mutation-Positive Group \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBased on the sequencing results, the cohort was divided into two groups: the mutation-positive (MP) group (16/46) and the mutation-negative (MN) group (30/46), as shown in Table 3. Considering the stringent selection criteria and reclassification of DCM according to the ACMG guidelines, the genetic analysis suggested that these 16 patients could be classified as either \u0026lsquo;pathogenic\u0026rsquo; or \u0026lsquo;likely pathogenic\u0026rsquo; mutant carriers. All carriers were identified with only one pathogenic or likely pathogenic mutation in DCM-associated genes (Figure 1). We identified 10 genes with disease causing heterozygous mutations, including those with integral sarcomere functions like titin (\u003cem\u003eTTN\u003c/em\u003e) [(OMIM *604145), (n=6, 37.5%)], myosin heavy chain 7 (\u003cem\u003eMYH7\u003c/em\u003e) [(OMIM *613426) (n=1, 6.25%)], troponin T2 (\u003cem\u003eTNNT2\u003c/em\u003e) [(OMIM *601494) (n=1, 6.25%)], Nexilin (\u003cem\u003eNEXN\u003c/em\u003e) [(OMIM* 613122) (n=1, 6.25%)], troponin I3 (\u003cem\u003eTNNI3\u003c/em\u003e) [(OMIM*613286) (n=1, 6.25%)], cytoskeletal structure-related genes like filamin-C (\u003cem\u003eFLNC\u003c/em\u003e) [(OMIM*617047) (n=1, 6.25%)], vinculin (\u003cem\u003eVCL\u003c/em\u003e) [(OMIM*611407) (n=1, 6.25%)], and other genes like RNA binding motif Protein 20 (\u003cem\u003eRBM20\u003c/em\u003e) [(OMIM*613172) (n=2, 12.5%)], NK2 homeobox 5 (\u003cem\u003eNKX2-5\u003c/em\u003e) [(OMIM:108900) (n=1, 6.25%)] and PR domain containing 16 (\u003cem\u003ePRDM16\u003c/em\u003e) [(OMIM*615373) (n=1, 6.25%)]. Table 4 summarizes the main clinical features and the details of identified variants in DCM patients. Excluding 3 patients with familial mutations in \u003cem\u003eTTN\u003c/em\u003e, \u003cem\u003eMYH7\u003c/em\u003e and \u003cem\u003eNEXN\u003c/em\u003e genes, 5 de novo variants were identified in \u003cem\u003eNKX2-5\u003c/em\u003e, \u003cem\u003eTNNI3\u003c/em\u003e, \u003cem\u003ePRDM16,\u003c/em\u003e and \u003cem\u003eRBM20\u003c/em\u003e (n=2) genes. Among the identified 16 gene mutations (missense-5, non-sense-5, frameshift-4 and splice site-2), 2 same mutations were identified in a pair of monozygotic (MZ) twin patients, and 10 (62.5%) other mutations were novel.,\u003c/p\u003e\n\u003cp\u003eIn total, we identified 6 different (5 novels) \u003cem\u003eTTN \u003c/em\u003etruncation variants, including 3 nonsense, 1 frameshift, and 2 splice-site variants, in 13% of patients (Table 4). \u0026nbsp;Furthermore, we mapped the identified variants to protein domains of \u003cem\u003eTTN\u003c/em\u003e gene (Figure 3a), which showed consistent results with previous reports. Notably, 4 variants were in\u0026nbsp;I-band, and the remaining 2 in A-band and M-band\u0026nbsp;regions, respectively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGenotype and Clinical Phenotype Analyses \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe phenotypic severity of these patients at presentation was measured by LVEDD Z-score, LVEF, and serum proBNP level. There were no significant\u0026nbsp;differences\u0026nbsp;in distribution based on sex (P=0.202), age (P=0.23), LVEF (P=0.935), LVEDD Z-score (P=0.42), and serum proBNP level (P=0.115) between MP and MN groups. The MP group probands exhibited lower phenotypic severity (echocardiographic parameters) than MN group DCM probands, with the same LVEF of 28.5% and LVEDD Z-score of 6.4 versus 7.08, respectively. Also, we observed a trend that the\u0026nbsp;onset\u0026nbsp;age\u0026nbsp;(median 9.5 months) in\u0026nbsp;MP group was slightly\u0026nbsp;higher\u0026nbsp;than\u0026nbsp;that\u0026nbsp;in\u0026nbsp;the\u0026nbsp;MN\u0026nbsp;group (median 6 months). Nine MP patients developed DCM before 12 months of age, and the age distribution was between 1 month and 13 years.\u003c/p\u003e\n\u003cp\u003eDespite the observation of better echocardiographic parameters and seemingly better phenotypes at presentation in MP group patients, there was no significant difference in the outcome (the number of deceased patients, P=0.145) and LVEF recovery patients, P=0.665) between\u0026nbsp;the\u0026nbsp;two\u0026nbsp;groups during the follow-up of median time of 12.5 months (P=0.972). Survival curves free from death and recovery also showed similar results (Figure 3). 37.5% (6/16) of MP DCM patients eventually suffered from heart failure related death compared to only 13% (4/30) of the MN group. Although no significant differences in survival free of death (P= 0.093) were documented, however, there was a trend toward a worse prognosis in our patients at advanced ages (Figure 2a) when compared to the MN patients. The outcome of cardiac death occurred in patients with \u003cem\u003eTTN\u003c/em\u003e truncating mutants (c.50065C\u0026gt;T, c.98421_98422insGG, c.37454-2A\u0026gt;T), and \u003cem\u003eNKX2-5\u003c/em\u003e (c.242delA),\u003cem\u003e TNNT2 \u003c/em\u003e(c.422G\u0026gt;A), \u003cem\u003eTNNI3\u003c/em\u003e (c.544G\u0026gt;A) mutations. Notably, 5 out of 6 disease causing mutations belong to sarcomeric genes (\u003cem\u003eTTN\u003c/em\u003e=3, \u003cem\u003eMYH7,\u003c/em\u003e\u003cem\u003eTNNT2\u003c/em\u003e, \u003cem\u003eTNNI3\u003c/em\u003e).\u003c/p\u003e\n\u003cp\u003eIn this study, a significant proportion of the patients exhibited marked improvement and better prognostic outcomes in response to heart failure treatment. In both groups, almost 50% of pediatric patients could recover (LVEF above 50%). There was a trend toward better recovery in MN patients at advanced ages (Figure 2b).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eTTN\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e Truncation Variants in Pediatric DCM Patients \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHere, we describe the clinical and genetic characteristics of 4 probands with 6 \u003cem\u003eTTN \u003c/em\u003emutations (as summarized in Table 4).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eP2\u003c/strong\u003e: A 12 years-old girl presented with dyspnea and fatigue. Her chest x-ray revealed enlarged heart size, and echocardiography showed LVEDD value 5.86cm and LVEF of 27%. Her brother died of severe congenital heart disease at \u0026lt;1 year age. Her LVEF was recovered to 58% after treatment. A novel \u0026lsquo;likely pathogenic\u0026rsquo; nonsense heterozygous truncation mutation (c.43298T\u0026gt;G, p.Leu14433*) in \u003cem\u003eTTN \u003c/em\u003egene was confirmed in the proband and her mother by genetic analysis (Figure 4b). But her mother had no symptoms.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eP4\u003c/strong\u003e: A 12 years-old boy with DCM performed a cardiology outpatient clinical evaluation due to the sudden onset of shortened breath with abdominal pain, cough, chest tightness, and fatigue. The proband performed an electrocardiogram (ECG) showing the left anterior fascicular block. Also, he exhibited severely elevated plasmatic transaminases (AST = 275U/L, ALT = 881U/L). The abdominal CT elsewhere revealed ascites, pleural effusion. Remarkably, the plasmatic NT-proBNP level was also drastically high (960.4pg/ml) (normal values less than 125pg/ml at the proband\u0026rsquo;s age). He also performed an electrocardiogram of the left\u0026nbsp;anterior\u0026nbsp;fascicular\u0026nbsp;block and echocardiography showing LVEF of 20%, LVEDD of 7.29cm. After receiving the regimen of spironolactone 40mg/day, captopril 8.3mg/day, furosemide 40mg/day, digoxin 0.25mg/day, potassium chloride sustained release tablets 6000mg/day for 13 days, a repeated echocardiography showed a more severe dilated left ventricle (7.45cm) and a suspicion for left ventricular apex noncompaction. Three months after diagnosis of DCM, he was hospitalized again and died of ventricular tachycardia at a young age. NGS and Sanger sequencing confirmed the \u0026lsquo;pathogenic\u0026rsquo;\u003cem\u003e TTN\u003c/em\u003e (c.50065C\u0026gt;T, p.Arg16689*) variant in the proband and his mother (Figure 4b). His mother had no symptoms, and she refused to perform echocardiography. For the first time, a pathogenic variant in \u003cem\u003eTTN\u003c/em\u003e was associated with the DCM phenotype.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eP8: \u003c/strong\u003eA 10 years-old girl, who suffered from DCM for about 3 years and showed no response to heart failure medication, died of heart failure and pneumonia. At the onset, she had an increased serum phosphocreatine kinase (up to 2900u/L) level, and her ECG showed premature\u0026nbsp;ventricular\u0026nbsp;contractions. We identified a novel \u0026lsquo;likely pathogenic\u0026rsquo; frameshift mutation in \u003cem\u003eTTN\u003c/em\u003e (c.98421_98422insGG, p.I30808Pfs * 7) by NGS analysis in the proband and her father. Her father didn\u0026rsquo;t show any symptoms. Involvement of skeletal myopathy was suspected in this patient because of increased phosphocreatine kinase level. The skeletal myopathy was then identified by muscle biopsy (failing to record the pathologic result). This suggests that this variant can cause disease in both heart and skeletal muscles.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eP13:\u003c/strong\u003e A girl diagnosed with DCM at the age of 3 months had an autosomal dominant family history of DCM. Her maternal grandfather (diagnosed at 36 and died at 52 years), the brother of the grandfather (diagnosed at 42 and died at 46 years), and their sister (diagnosed at 44 and died at 52 years) died of DCM. The proband presented with shortness of breath and atrial\u0026nbsp;tachycardia. She was given a treatment of dopamine cardiotonic, furosemide, spironolactone, amiodarone, and captopril. Unfortunately, 6 months later Her mother felt shortness of breath after activity and performed echocardiography elsewhere, exhibiting LVEF=29% and LVEDD=6.8cm. After 3 years of follow-up, the proband could recover her LVEF to 62% with no signs of arrhythmia. But her mother still receives drug treatment and has not been recovered yet. By trio WES method, we identified a novel truncating \u0026lsquo;likely pathogenic\u0026rsquo; mutation in \u003cem\u003eTTN\u003c/em\u003e gene (c.105541A\u0026gt; T, p.K35181X) in the proband and her mother, but not in her father and 8-years old brother (Figure 3), who both had normal echocardiography parameters.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eRBM20\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e Gene Mutation in Pediatric DCM \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eP6 \u003c/strong\u003eand\u003cstrong\u003e P7\u003c/strong\u003e, monozygotic (MZ) twin brothers (a kinship coefficient of 0.4901), were diagnosed with DCM with LVEF 29% and 31%, respectively at the age of 12 years (the interval time of onset was 9 months). They both felt nausea, chest tightness, and shortness of breath. Both ECG showed ventricular premature beats. The MZ twin was administered with standard heart failure medication. After seven years of follow-up, the LVEF of the two patients were 56% and 55%, respectively, and remain asymptomatic. By WES screening, a \u0026lsquo;pathogenic\u0026rsquo; de novo mutation c.2746G\u0026gt;A (p.E916K) in \u003cem\u003eRBM20\u003c/em\u003e gene was identified. The missense mutation was absent from controls (1000G, ESP, and ExAC-ALL),\u0026nbsp;and was predicted to be \u0026lsquo;pathogenic\u0026rsquo; by PolyPhen2,\u0026nbsp;SIFT databases. The amino acid p.E916 is highly conserved across vertebrate species (Figure 5C). We confirmed this missense mutation by Sanger sequencing in the twin patients\u0026nbsp;but not in their parents \u003cstrong\u003e(\u003c/strong\u003eFigure 5B).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eDCM is a common type of pediatric heart disease leading to poor clinical outcomes and heart transplantation [\u003ca href=\"#_ENREF_29\"\u003e29\u003c/a\u003e, \u003ca href=\"#_ENREF_30\"\u003e30\u003c/a\u003e]. In this cohort, with a presentation of mean LVEF of 28.5% and the mean LVEDD Z-score of 7.02, DCM presented a severe disease phenotype. 67.4% of patients (31/46) manifested DCM before 1 year of age. Genetic factors play an important role in DCM pathogenesis. However, genetic discovery and prognostic understanding are still a challenge for DCM therapy. Hence, we sought to discover the landscape of genetic variations in pediatric patients with DCM. In this study, among 46 pediatric patients with DCM, we found that 16 (34.8%) patients carried at least one pathogenic or likely pathogenic mutation in a disease-causing gene. Consistent with previous studies, mutations in sarcomere genes were detected most frequently in all these DCM patients [\u003ca href=\"#_ENREF_31\"\u003e31\u003c/a\u003e]. The prevalence of pathogenic mutations seemed to be similar as in recently published cohorts [\u003ca href=\"#_ENREF_32\"\u003e32\u003c/a\u003e, \u003ca href=\"#_ENREF_33\"\u003e33\u003c/a\u003e]. There was no difference in clinical presentations and prognosis, no matter whether there were gene mutations or not. Mutations were identified frequently in childhood-onset of DCM, especially in sarcomeric genes. Importantly, \u003cem\u003eTTN\u003c/em\u003e-related mutations were found in 10 out of 16 MP patients. \u003cem\u003eTTN\u003c/em\u003e truncating mutations account for 12%-27% of all adult DCM cases, suggesting the importance of diagnostic sequencing [\u003ca href=\"#_ENREF_34\"\u003e34-38\u003c/a\u003e]. However, the \u003cem\u003eTTN\u003c/em\u003e truncating mutations have been rarely identified in pediatric patients previously [\u003ca href=\"#_ENREF_39\"\u003e39-41\u003c/a\u003e]. Also, recent studies in pediatric DCM have shown similar results [\u003ca href=\"#_ENREF_14\"\u003e14\u003c/a\u003e]. Notably, a genetic analysis in a cohort of 66 severe childhood cardiomyopathy, including 37 DCM cases, could not identify any \u003cem\u003eTTN\u003c/em\u003e truncating mutations in these pediatric patients [\u003ca href=\"#_ENREF_22\"\u003e22\u003c/a\u003e]. Likewise, another study involving 30 Chinese pediatric subjects with sporadic DCM pathology also could not find any pathogenic \u003cem\u003eTTN\u003c/em\u003e gene mutations [\u003ca href=\"#_ENREF_37\"\u003e37\u003c/a\u003e]. However, in another study only one pathogenic \u003cem\u003eTTN \u003c/em\u003etruncating variant has been identified in a 16 years-old boy among 36 pediatric DCM patients [\u003ca href=\"#_ENREF_38\"\u003e38\u003c/a\u003e]. Obvious differently from low prevalence of \u003cem\u003eTTN \u003c/em\u003etruncating mutants, we identified 6 different \u003cem\u003eTTN\u003c/em\u003e truncating variants in 6 (13%) of 46 pediatric patients.\u003c/p\u003e\n\u003cp\u003eThe prognosis of DCM cases with \u003cem\u003eTTN\u003c/em\u003e truncating mutations has been found to be different and conflicting in adult studies from moderate to severe outcomes. Notably, DCM patients with \u003cem\u003eTTN\u003c/em\u003e mutations have shown a good response to treatment [\u003ca href=\"#_ENREF_39\"\u003e39\u003c/a\u003e]. A cohort of 70 patients with end-stage DCM has shown recovery after left ventricle assist device implantation [\u003ca href=\"#_ENREF_40\"\u003e40\u003c/a\u003e]. While another study has shown \u003cem\u003eTTN\u003c/em\u003e mutation-positive patients frequently present severe cardiomyopathy and a worse 5-year prognosis [\u003ca href=\"#_ENREF_4\"\u003e4\u003c/a\u003e].\u003c/p\u003e\n\u003cp\u003eThe different clinical outcomes in \u003cem\u003eTTN\u003c/em\u003e MP patients were also observed in our findings. Three patients with \u003cem\u003eTTN\u003c/em\u003e mutations (c.18230-1G\u0026gt;A, c.43298T\u0026gt;G, c.105541A\u0026gt;T) recovered after medical treatment with no further symptom, while 3 other patients harboring \u003cem\u003eTTN\u003c/em\u003e mutations (c.50065C\u0026gt;T, c.98421_98422insGG, c.37454-2A\u0026gt;T) showed no response to treatment and died from heart failure, suggesting clinical heterogeneity. The conflicting prognosis prompts that apart from the identified genetic factors, post-transcriptional, environmental, hormonal, and other factors could also modify the rate of disease progression. Therefore, it might be difficult to predict the clinical outcomes in pediatric DCM cases based on \u003cem\u003eTTN\u003c/em\u003e truncating mutations alone.\u003c/p\u003e\n\u003cp\u003eIt has been found that the penetrance of\u003cem\u003e\u0026nbsp;TTN\u0026nbsp;\u003c/em\u003etruncating mutations can reach up to 100% by the age of 70 years [\u003ca href=\"#_ENREF_42\"\u003e42\u003c/a\u003e], which leads to discordant segregation with phenotype, and the same variant has also been detected in the unaffected relatives. In some pedigrees of unaffected relatives, especially in familial DCM, a clinical follow-up with aging should be carried up. The age onset of girl \u003cstrong\u003eP13 \u003c/strong\u003e(3 months) with \u003cem\u003eTTN\u003c/em\u003e truncating mutation (c.105541A\u0026gt;T, p.K35181X) was obviously different from her mother (23 years) and her grandfather (36 years), suggesting the possible involvement of some other factors influencing DCM pathogenesis.\u003c/p\u003e\n\u003cp\u003eIn addition, we identified a pathogenic RBM20 variant (p.E916K) in the twin patients (\u003cstrong\u003eP6 \u003c/strong\u003eand\u003cstrong\u003e P7\u003c/strong\u003e) with pediatric DCM. RBM20 mutations have been reportedly associated with cardiomyopathy [\u003ca href=\"#_ENREF_43\"\u003e43\u003c/a\u003e]. Notably, the variant c.2746G\u0026gt;A (p.E916K) of RBM20 mutant identified in this study was located on exon11, a known hot spot for cardiomyopathy-associated mutations (Figure 6). However, the mechanistic relation of RBM20 mutations with DCM onset is still unclear.\u003c/p\u003e\n\u003cp\u003eA de novo mutation in PRDM16 gene in an 8-months girl (\u003cstrong\u003eP9\u003c/strong\u003e) was identified to be associated with pediatric DCM. Previously known mutants of this gene are mostly missense mutations; however, a nonsense mutation leading to functional loss of PRDM16 was detected in this case. The role of \u003cem\u003ePRDM16 \u003c/em\u003egene mutations could be very important, warranting further studies to identify its pathogenic mechanism.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLimitations \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study suffers from the following limitations: 1) it was a single-centered, retrospective, and a small cohort study; 2) follow-up time was not long enough to estimate the long-term outcomes; 3) clinical assessment was highly recommended for family members of the probands, but only a minority of the relatives were willing to participate in this evaluation, so gene mutation carriers of a family could be underestimated in our cohort; 4) bioinformatic prediction could give us some useful information about the pathogenicity of mutants associated with DCM, however, it cannot reflect the real pathobiology of the mutants in the cardiac myocytes.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eDCM is a genetically heterogeneous disease in children and adults. Using NGS analysis, we could detect that more than one-third of cases of DCM were caused by genetic mutations in genes related to the structure or function of sarcomeric, desmosomal and cytoskeletal proteins as well as decipher their genotype-phenotype correlations in pediatric DCM patients. Here, we discovered 6 \u003cem\u003eTTN\u003c/em\u003e truncating mutations (5 novel) correlated with severe disease phenotypes. Furthermore, we found 16 mutations in 10 genes in 16 patients that were likely to be associated with DCM pathogenesis. Most pediatric patients were diagnosed with DCM before 1 year of age. Also, most deaths occurred within the first year of life after diagnosis. The cardiac death occurred in patients harboring mutations in \u003cem\u003eTTN \u003c/em\u003e(3), \u003cem\u003eNKX2-5\u003c/em\u003e(1), \u003cem\u003eTNNT2\u003c/em\u003e(1) genes. Hence, this study advances the genetic understanding of pediatric DCM and highlights certain genetic defects with severe clinical courses. To the best of our knowledge, this is the first study reporting that the presence of \u003cem\u003eTTN\u003c/em\u003e truncating mutations could be associated with the onset and development of DCM in pediatric patients. Further studies are needed to define the mechanisms by which pathogenic \u003cem\u003eTTN\u003c/em\u003e variants affect outcomes in pediatric and adult patients with DCM.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by the Natural Science Foundation of China (Grant number: 81873498); Natural Science Foundation of Shandong Province (Grant number: ZR2019MH015); Jinan Science and Technology Development Plan (Grant number 201805020); and Special Expert of Taishan Scholars (Grant number: TS201511099).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data and materials are available upon request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCode availability: \u003c/strong\u003eN/A\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. YW and BH collected patient data and prepared the manuscript. YF, XY, JL, and JW contributed to the clinical understanding of the case and revision of the manuscript. YY, HY, LZ, and JZ analyzed and interpreted the genetic data and surveyed the literature relevant to the mutations. All authors reviewed the results and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur study received ethics approval (NSFC：NO.2018-115) from the ethic committee of Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University.\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e: N/A.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors and study participants declare their unconditional consent toward publication of this manuscript and its associated data in the peer-reviewed journal.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eACMG, American College of Medical Genetics and Genomics. ALT, Alanine transaminase. AST, Aspartate transaminase\u003cem\u003e. \u003c/em\u003eCT, Computed Tomography. DCM, dilated cardiomyopathy. \u003cem\u003eFLNC, \u003c/em\u003efilamin C.\u0026nbsp;HGMD, Human Gene Mutation Database. LVEDD left ventricular end-diastolic diameter. LVEF, left ventricular ejection fraction. LVNC, left ventricular noncompaction. \u003cem\u003eMYH7,\u003c/em\u003e \u0026szlig;-Myosin Heavy Chain gene, MP, mutation positive. MN, mutation negative. \u003cem\u003eNEXN,\u003c/em\u003e Nexilin F-Actin Binding Protein gene. \u003cem\u003eNKX2-5,\u003c/em\u003e NK2 homeobox5. NGS, Next Generation Sequencing. NT-proBNP, N-terminal pro-brain-natriuretic peptide. \u003cem\u003ePRDM16,\u003c/em\u003e positive regulatory domain16. \u003cem\u003eRBM20,\u003c/em\u003e RNA-binding protein20. \u003cem\u003eTNNI3,\u003c/em\u003e troponin I. \u003cem\u003eTNNT2,\u003c/em\u003e troponin T. \u003cem\u003eTTN, \u003c/em\u003etitin. \u003cem\u003eVCL,\u003c/em\u003e vinculin. WES, Whole-Exome Sequencing.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eTaylor MR, Carniel E, Mestroni L (2006) Cardiomyopathy, familial dilated. Orphanet J Rare Dis 1:27. \u003ca href=\"https://doi.org/10.1186/1750-1172-1-27\"\u003ehttps://doi.org/10.1186/1750-1172-1-27\u003c/a\u003e.\u003c/li\u003e\n\u003cli\u003ePuggia I, Merlo M, Barbati G, Rowland TJ, Stolfo D, Gigli M, Ramani F, et al. (2016) Natural history of dilated cardiomyopathy in children. J Am Heart Assoc 5(7). \u003ca href=\"https://doi.org/10.1161/jaha.116.003450\"\u003ehttps://doi.org/10.1161/jaha.116.003450\u003c/a\u003e.\u003c/li\u003e\n\u003cli\u003eNugent AW, Daubeney PE, Chondros P, Carlin JB, Cheung M, Wilkinson LC, Davis AM, et al. (2003) The epidemiology of childhood cardiomyopathy in australia. 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Pediatr Cardiol 40(5):950-957. \u003ca href=\"https://doi.org/10.1007/s00246-019-02096-1\"\u003ehttps://doi.org/10.1007/s00246-019-02096-1\u003c/a\u003e.\u003c/li\u003e\n\u003cli\u003eZaklyazminskaya E, Mikhailov V, Bukaeva A, Kotlukova N, Povolotskaya I, Kaimonov V, Dombrovskaya A, et al. (2019) Low mutation rate in the ttn gene in paediatric patients with dilated cardiomyopathy - a pilot study. Sci Rep 9(1):16409. \u003ca href=\"https://doi.org/10.1038/s41598-019-52911-1\"\u003ehttps://doi.org/10.1038/s41598-019-52911-1\u003c/a\u003e.\u003c/li\u003e\n\u003cli\u003eJansweijer JA, Nieuwhof K, Russo F, Hoorntje ET, Jongbloed JD, Lekanne Deprez RH, Postma AV, et al. (2017) Truncating titin mutations are associated with a mild and treatable form of dilated cardiomyopathy. Eur J Heart Fail 19(4):512-521. \u003ca href=\"https://doi.org/10.1002/ejhf.673\"\u003ehttps://doi.org/10.1002/ejhf.673\u003c/a\u003e.\u003c/li\u003e\n\u003cli\u003eFelkin LE, Walsh R, Ware JS, Yacoub MH, Birks EJ, Barton PJ, Cook SA (2016) Recovery of cardiac function in cardiomyopathy caused by titin truncation. JAMA Cardiol 1(2):234-235. \u003ca href=\"https://doi.org/10.1001/jamacardio.2016.0208\"\u003ehttps://doi.org/10.1001/jamacardio.2016.0208\u003c/a\u003e.\u003c/li\u003e\n\u003cli\u003eAnderson JL, Christensen GB, Escobar H, Horne BD, Knight S, Jacobs V, Afshar K, et al. (2020) Discovery of titin gene truncating variant mutations and 5-year outcomes in patients with nonischemic dilated cardiomyopathy. Am J Cardiol 137:97-102. \u003ca href=\"https://doi.org/10.1016/j.amjcard.2020.09.026\"\u003ehttps://doi.org/10.1016/j.amjcard.2020.09.026\u003c/a\u003e.\u003c/li\u003e\n\u003cli\u003eKayvanpour E, Sedaghat-Hamedani F, Amr A, Lai A, Haas J, Holzer DB, Frese KS, et al. (2017) Genotype-phenotype associations in dilated cardiomyopathy: Meta-analysis on more than 8000 individuals. Clin Res Cardiol 106(2):127-139. \u003ca href=\"https://doi.org/10.1007/s00392-016-1033-6\"\u003ehttps://doi.org/10.1007/s00392-016-1033-6\u003c/a\u003e.\u003c/li\u003e\n\u003cli\u003eWatanabe T, Kimura A, Kuroyanagi H (2018) Alternative splicing regulator rbm20 and cardiomyopathy. Front Mol Biosci 5:105. \u003ca href=\"https://doi.org/10.3389/fmolb.2018.00105\"\u003ehttps://doi.org/10.3389/fmolb.2018.00105\u003c/a\u003e.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:13px;\"\u003eTable 1\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"font-size:13px;\"\u003eAge Distribution of Pediatric Patients with DCM Onset.\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width: 2.9e+2pt;margin-left:49.65pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 85.05pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eAge group\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eyears\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 120.45pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:center;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eN\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 85.05pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eDeath (n)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eduring follow-up\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003efemales\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.75pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003emales\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e\u0026lt;1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e17\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.75pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e14\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e1-3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.75pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e3-6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.75pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e0\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e0\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e6-10\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.75pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e0\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e10-13\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.75pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eTotal\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e26\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.75pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e20\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1.5pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e10\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:13px;color:black;\"\u003eTable 2\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"font-size:13px;\"\u003eClinical Characterization of Pediatric DCM Patients Between Female and Male Onset and Latest Outcomes.\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width: 3.7e+2pt;margin-left:49.65pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 134.65pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 170.1pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e\u0026nbsp;All patients, n=46\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 63.8pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP-value\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 92.15pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eFemales, n=26\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eMales, n=20\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 134.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eAge, months (range)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92.15pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e7(1-144)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e6(1-156)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e0.657\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 134.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eLVEF% (range)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92.15pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e30(20-42)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e27.5(17-35)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e0.355\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 134.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eLVEDD Z-score (range)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92.15pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e7.46(2.36-13.65)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e6.75(3.01-12.87)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e0.807\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 134.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNT-proBNP pg/ml (range)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92.15pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e15466(84.55-35000)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e6485(960-35000)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e0.594\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 134.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eDeceased during study, n (%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92.15pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e6(23.1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e4(20)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e0.059\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 134.65pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eRecover during study, n (%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 92.15pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e15(60)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e10(50)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1.5pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e0.608\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"font-size:13px;line-height:200%;color:black;\"\u003eAbbreviations: LVEF, left ventricular ejection fraction; LVEDD, left ventricular end diastolic diameter (Z-score, normal reference range between -2 standard deviation [SD] and +2 SD);\u0026nbsp;\u003c/span\u003e\u003cspan style=\"font-size:13px;line-height:200%;\"\u003eNT-proBNP\u003c/span\u003e\u003cspan style=\"font-size:13px;line-height:200%;\"\u003e, N-terminal fragment of pro-b-natriuretic peptide.\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;line-height:200%;'\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:13px;\"\u003eTable 3\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"font-size:13px;\"\u003eClinical Characteristics of Mutation-Positive and Mutation-Negative Groups.\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width: 4.7e+2pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 141.75pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003eclinical characteristics\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eAll (n=46)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eMutation positive (n=16)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.25pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eMutation negative\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;text-indent:42.0pt;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e(n=30)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP-value\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 141.75pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eSex\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.25pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border: none;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e0.202\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 141.75pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eMale (n%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e20(43.5)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e9(56,25)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.25pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e11(36.7)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border: none;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 141.75pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eFemale (n%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e26(56.5)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e7(43.75)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.25pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e19(63.3)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 141.75pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eAge onset\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003emonths (range)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e6.5(1-156)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e9.5(1-156)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.25pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e6(1.5-108)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border: none;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e0.23\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 141.75pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;font-family:SimSun;color:black;\"\u003e＜\u003c/span\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e12\u0026nbsp;months (n%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e31(67.4)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e9(56.2)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.25pt;border-top: none;border-bottom: none;border-left: none;border-image: initial;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e22(73.3)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border: none;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 141.75pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e12-156 months(n%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e15(32.6)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e7(43.8)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.25pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e8(26.7)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 141.75pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eLVEF% (range)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e28.5(17-42)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e28.5(20-33)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.25pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e28.5(17-42)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e0.935\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 141.75pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eLVEDD Z-score (range)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e7.02(2.36-13.65)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e6.4(3.6-13.65)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.25pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e7.08(2.36-12.87)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e0.42\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 141.75pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNT-proBNP pg/ml(range)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e14406(54.5-35000)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e6276(960.4-35000)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.25pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e16305(84.5-35000)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e0.115\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 141.75pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eFollow-up (months) (range)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e12.5(1-84)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e12(1-84)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.25pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e12.5(1-69)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e0.972\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 141.75pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eDeceased during study, n (%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e10(21.7\u003c/span\u003e\u003cspan style=\"font-size:16px;font-family:SimSun;color:black;\"\u003e）\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e6(37.5)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.25pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e4(13.3)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e0.06\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 141.75pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eRecover during study, n (%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e25(54.3)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85.05pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e8(50)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99.25pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e17(56.7)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1.5pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e0.665\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"font-size:13px;line-height:200%;\"\u003eAbbreviations: LVEF, left ventricular ejection fraction; LVEDD, left ventricular end diastolic diameter (Z-score, normal reference range between -2 standard deviation [SD] and +2 SD);\u0026nbsp;\u003c/span\u003e\u003cspan style=\"font-size:13px;line-height:200%;\"\u003eNT-proBNP, N-terminal pro-brain natriuretic peptide.\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;line-height:200%;'\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size:16px;\"\u003eTable 4\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"font-size:16px;\"\u003eClinical and Genetic Characteristics of Patients Identified in Mutation-Positive Group.\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width: 6.9e+2pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.6pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003ePatient#\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.5pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eSex\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eAge of Onset\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eFamily\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eHistory\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eTime to Death after diagnosis\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eModern age\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.65pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eLVEF recovery\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e(above50%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eArrhythmia\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.45pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eGene\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eVariant\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e(cDNA; Protein)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.55pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eMethod\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePrevious Reports of\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ethe Variant\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP1\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.5pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eMale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e12months\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e3years\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eYes\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003esinus\u0026nbsp;rhythm\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.45pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cem\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eTTN\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ec.18230-1G\u0026gt;A splicing\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.55pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePanel 2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP2\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.5pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eFemale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e12years\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e14years\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eYes\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003epremature\u0026nbsp;ventricular\u0026nbsp;contractions with low\u0026nbsp;voltage\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.45pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cem\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eTTN\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ec.43298T\u0026gt;G p.Leu14433*\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.55pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePanel 2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP3\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.5pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eFemale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e5months\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e1.9years\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eYes\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003etransient\u0026nbsp;junctional\u0026nbsp;rhythm\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.45pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cem\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eFLNC\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ec.4249_4250del\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ep.Y1417*fs\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.55pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePanel 2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP4\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.5pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eMale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e12years\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e3months\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eleft\u0026nbsp;anterior\u0026nbsp;fascicular\u0026nbsp;block\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.45pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cem\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eTTN\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ec.50065C\u0026gt;T\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ep.Arg16689*\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.55pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePanel 2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e[\u003c/span\u003e\u003ca href=\"#_ENREF_21\" title=\"Miszalski-Jamka, 2017 #148\"\u003e\u003cspan style=\"font-size:16px;\"\u003e21\u003c/span\u003e\u003c/a\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP5\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.5pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eMale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e10months\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e4months\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003esinus\u0026nbsp;rhythm\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.45pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cem\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNKX2-5\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ec.242delA\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ep.K81Sfs*95\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.55pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePanel 1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP6\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.5pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eMale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e13years\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e21years\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eYes\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eLow\u0026nbsp;voltage, premature\u0026nbsp;ventricular\u0026nbsp;contractions\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.45pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cem\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eRBM20\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ec.2746G\u0026gt;A\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ep.E916K\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.55pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eWES\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e[\u003c/span\u003e\u003ca href=\"#_ENREF_22\" title=\"Parikh, 2019 #149\"\u003e\u003cspan style=\"font-size:16px;\"\u003e22\u003c/span\u003e\u003c/a\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP7\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.5pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eMale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e13years\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e21years\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eYes\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eLow\u0026nbsp;voltage\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.45pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cem\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eRBM20\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ec.2746G\u0026gt;A\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ep.E916K\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.55pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eWES\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e\u0026nbsp;\u003c/span\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e[\u003c/span\u003e\u003ca href=\"#_ENREF_22\" title=\"Parikh, 2019 #149\"\u003e\u003cspan style=\"font-size:16px;\"\u003e22\u003c/span\u003e\u003c/a\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.5pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eFemale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e10years\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e36months\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003epremature\u0026nbsp;ventricular\u0026nbsp;contractions\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.45pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cem\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eTTN\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ec.98421_98422insGG\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ep.I32808Pfs*7\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.55pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePanel 1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP9\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.5pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eFemale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e8months\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e4years\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eYes\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003epremature\u0026nbsp;ventricular\u0026nbsp;contractions\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.45pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cem\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePRDM16\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ec.764C\u0026gt;G\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ep.S255X\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.55pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePanel 1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP10\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.5pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eMale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e1month\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eBrother, DCM\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e7months\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eatrial premature beats\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.45pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cem\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eMYH7\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ec.2713T\u0026gt;C\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ep.C905R\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.55pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eWES\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e[\u003c/span\u003e\u003ca href=\"#_ENREF_23\" title=\"Hoedemaekers, 2013 #150\"\u003e\u003cspan style=\"font-size:16px;\"\u003e23\u003c/span\u003e\u003c/a\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP11\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.5pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eFemale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e9months\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e4years\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003epremature\u0026nbsp;ventricular\u0026nbsp;contractions\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.45pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cem\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eVCL\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ec.142C\u0026gt;T\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ep.Q48X\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.55pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePanel 1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP12\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.5pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eFemale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e1.5months\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e1month\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003esinus\u0026nbsp;rhythm\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.45pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cem\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eTTN\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ec.37454-2A\u0026gt;T\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003esplicing\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.55pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePanel 1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP13\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.5pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eFemale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e3months\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eMother and grandfather, DCM\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e4years\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eYes\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eatrial\u0026nbsp;tachycardia\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.45pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cem\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eTTN\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ec.105541A\u0026gt; T\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ep.K35181X\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.55pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eWES\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP14\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.5pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eMale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e3months\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eBrother, heart enlarge and death\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e6.5years\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eYes\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eatrial premature beats\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.45pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cem\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNEXN\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ec.1139_1142del\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ep.E380Dfs*2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.55pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePanel 1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP15\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.5pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eMale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e18months\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e1month\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e\u0026nbsp;sinus rhythm\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.45pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cem\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eTNNT2\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ec.422G\u0026gt;A\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ep.R141Q\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.55pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePanel 1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e[\u003c/span\u003e\u003ca href=\"#_ENREF_24\" title=\", 2008 #151\"\u003e\u003cspan style=\"font-size:16px;\"\u003e24\u003c/span\u003e\u003c/a\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e,\u0026nbsp;\u003c/span\u003e\u003ca href=\"#_ENREF_25\" title=\"Cuenca, 2016 #152\"\u003e\u003cspan style=\"font-size:16px;\"\u003e25\u003c/span\u003e\u003c/a\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP16\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.5pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eMale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e3.5months\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e2monthss\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.65pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003epremature\u0026nbsp;ventricular\u0026nbsp;contractions\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.45pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cem\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eTNNI3\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ec.544G\u0026gt;A\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ep.E182K\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42.55pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eWES\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113.4pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1.5pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e[\u003c/span\u003e\u003ca href=\"#_ENREF_26\" title=\"Lakdawala, 2012 #153\"\u003e\u003cspan style=\"font-size:16px;\"\u003e26-28\u003c/span\u003e\u003c/a\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003eContinued\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width: 6.4e+2pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.65pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003ePatient#\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eMutation\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003etype\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eDe Novo\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eMutation\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eGnomAD\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eSIFT\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eAnd score\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eMT and score\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePP2 and score\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eGERP++ and score\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eREVEL\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;border-top: 1.5pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eACMG Variant Classification\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP1\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eSplicing\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eUnknown\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eD (1)\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eC (5.95)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eLikely pathogenic\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePVS1; PM2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP2\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNonsense\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eA (1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eC (5.56)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eLikely pathogenic\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePVS1; PM2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eFrameshift\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eLikely pathogenic\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePVS1; PM2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNonsense\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eA (1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eC (5.08)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003epathogenic\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePVS1; PM3_Strong;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePM2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP5\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eFrameshift\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eYes\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eLikely pathogenic\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePVS1; PM2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eMissense\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eYes\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eD (0.024)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eN (0.849)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP (0.874)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eC (4.71)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eB (0.244)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eLikely pathogenic\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePS4; PM2; BP4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP7\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eMissense\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eYes\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eD (0.024)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eN (0.849)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP (0.874)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eC (4.71)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eB (0.244)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eLikely pathogenic\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePS4; PM2; BP4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eFrameshift\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eLikely pathogenic\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePVS1; PM2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP9\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNonsense\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eYes\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eA (1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eC (3.39)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eLikely pathogenic\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePVS1; PM2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP10\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eMissense\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eD (0)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eD (1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP (0.998)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eC (5.55)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eD (0.892)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePathogenic\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePM3_Strong; PM1, PM2, PM5, PP3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP11\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNonsense\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eA (1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eC (4.41)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eLikely pathogenic\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePVS1; PM2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP12\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eSplicing\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eUnknown\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eD (1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eC (4.34)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eLikely pathogenic\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePVS1; PM2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP13\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNonsense\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eA (1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eC (4.78)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eLikely pathogenic\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePVS1; PM2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP14\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eFrameshift\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eLikely pathogenic\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePVS1; PM2\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP15\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eMissense\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eNo\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e0.000008\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eD (0)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eD (1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP (0.999)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eC (4.28)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eD (0.501)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eLikely pathogenic\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePS1; PM1; PP3\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 49.65pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eP16\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eMissense\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eYes\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eT(0.364)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eD (1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77.95pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eB (0.005)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eC (4.72)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49.6pt;border-top: none;border-left: none;border-bottom: 1.5pt solid windowtext;border-right: 1pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eB (0.319)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1.5pt solid windowtext;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003eLikely pathogenic\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;'\u003e\u003cspan style=\"font-size:16px;color:black;\"\u003ePM3_Strong, PM2, BP4\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:4.0pt;margin-left:0in;font-size:14px;font-family:\"Times New Roman\",serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"font-size:13px;line-height:200%;color:black;\"\u003eACMG: American College of Medical Genetics and Genomics; CADD: combined annotation-dependent depletion scores; DCM: dilated cardiomyopathy; PM: pathogenic moderate; PP: pathogenic supporting; PS: pathogenic strong; BP: supporting benign; PVS: pathogenic ve\u003c/span\u003e\u003cspan style=\"font-size:13px;line-height:200%;\"\u003ery strong; SIFT: Sorting Intolerant from Tolerant tool; WES: whole-exome sequencing; panel 1: Sinopath genetic technology including 113 cardiac genes; panel 2: Novocardio genetic technology Co. Ltd (Beijing, China), including 101 cardiomyopathy-related genes. P6 and P7 were twin brothers.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eSIFT Sorts intolerant from tolerant (D, damaging; T, tolerant), PP2, polymorphism phenotyping v2 (D, damaging; P, possible damaging; B, benign), MT mutation taster (D, disease causing; A, disease causing automatic; N, polymorphism; P, polymorphism_automatic)\u003c/span\u003e\u003cspan style=\"font-size:13px;line-height:200%;font-family:SimSun;\"\u003e，\u003c/span\u003e\u003cspan style=\"font-size:13px;line-height:200%;\"\u003eGERP++ genomic evolutionary rate profiling (C, conserved; N, non-conserved), Revel (D, damaging; B, benign).\u003c/span\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Dilated cardiomyopathy, Next-generation sequencing, Pediatric patients, Titin, Mutation","lastPublishedDoi":"10.21203/rs.3.rs-511994/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-511994/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eDilated cardiomyopathy (DCM) is a myocardial disease characterized by bilateral or left ventricular cardiac dilation and systolic dysfunction leading to heart failure and sudden cardiac death in children. Most studies focus on the genetic alterations in DCM-related genes in adult populations; however, it remains enigmatic about the mutational landscape in pediatric DCM patients, especially in the Chinese population. We exploited the next-generation sequencing (NGS) technologies to genetically analyze 46 pediatric patients and to decipher the genotype-phenotype correlation in these patients\u0026rsquo; clinical outcomes. Our results indicated DCM-associated pathogenic mutations in 10 genes related to the structure or function of the sarcomere, desmosomal and cytoskeletal proteins. We also identified 6 pathogenic mutations (5 novel) in the titin (\u003cem\u003eTTN\u003c/em\u003e) gene leading to the formation of truncated \u003cem\u003eTTN\u003c/em\u003e protein variants in 6 (13%) out of 46 patients each. Furthermore, we investigated the correlations between \u003cem\u003eTTN\u003c/em\u003e gene mutation and clinical outcomes in these patients.\u003c/p\u003e \u003cp\u003e \u003cem\u003eConclusion\u003c/em\u003e: Our data suggest that one-third of cases of pediatric DCM are caused by genetic mutations. The role of \u003cem\u003eTTN\u003c/em\u003e variants should not be underestimated in pediatric DCM and age-dependent pathogenic penetrance of these genetic mutations needs to be considered in the case of familial DCM. Thus, NGS analysis can be applied to decode the yet unknown DCM etiological genetic factors in pediatric as well as adult patients.\u003c/p\u003e","manuscriptTitle":"Next-Generation Sequencing Screening Reveals Novel Genetic Variants for Dilated Cardiomyopathy in Pediatric Chinese Patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-05-17 17:17:46","doi":"10.21203/rs.3.rs-511994/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7012a71d-aa98-412f-8682-f5e1a8076738","owner":[],"postedDate":"May 17th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":4375116,"name":"Pediatrics"}],"tags":[],"updatedAt":"2022-01-18T10:04:43+00:00","versionOfRecord":{"articleIdentity":"rs-511994","link":"https://doi.org/10.1007/s00246-021-02698-8","journal":{"identity":"pediatric-cardiology","isVorOnly":false,"title":"Pediatric Cardiology"},"publishedOn":"2021-08-04 10:04:43","publishedOnDateReadable":"August 4th, 2021"},"versionCreatedAt":"2021-05-17 17:17:46","video":"","vorDoi":"10.1007/s00246-021-02698-8","vorDoiUrl":"https://doi.org/10.1007/s00246-021-02698-8","workflowStages":[]},"version":"v1","identity":"rs-511994","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-511994","identity":"rs-511994","version":["v1"]},"buildId":"FbvkV6FR0MCFSLy54lSbu","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}