A Comprehensive Follow-Up Study Identifying Diagnostic Evidences for Secondary Finding

Abstract Background：There was a lacking of clinical diagnostic evidence in follow-up studies for reporting of secondary variants in 59 genes in American College of Medical Genetics and Genomics recommendations for reporting secondary findings and various strategies were applied to interpret the secondary variants. Results: Out of 1330 participants performed whole-exome sequencing, we identified 15 families with convincing clinical evidence. After Sanger validation and a comprehensive clinical follow-up, 10 families with both convincing clinical evidence and convincing genetic evidence of hereditary variants were found. Detailed clinical presentations and related clinical evidence were collected. Conclusions: Our research is a comprehensive follow-up study to identify secondary variants with convincing genetic and clinical evidence and it could help improve the strategy of screening actionable secondary variants and contribute to translation of genetic findings into medical practice.