Clinical genome sequencing: three years’ experience at a tertiary children’s hospital

Introduction Genome sequencing (GS) may shorten the diagnostic odyssey for patients, but clinical experience with this assay in non-research settings remains limited. Texas Children’s Hospital began offering GS as a clinical test to admitted patients in 2020, providing an opportunity to study how GS is utilized, potential for misorders, and outcomes of testing. Methods We conducted a retrospective review of GS orders for admitted patients for a nearly 3-year period from March 2020 through December 2022. We gathered anonymized clinical data from the electronic health record to answer the study questions. Results The diagnostic yield over 97 admitted patients was 35%. The majority of GS clinical indications were neurologic or metabolic (61%) and most patients were in intensive care (58%). Tests were often characterized as misordered (56%), frequently due to redundancy with prior testing. Patients receiving GS without prior exome sequencing (ES) had higher diagnostic rates (45%) than the cohort as a whole. In two cases, GS revealed a molecular diagnosis that is unlikely to be detected by ES. Conclusions The performance of GS in clinical settings likely justifies its use as a first-line diagnostic test, but the incremental benefit for patients with prior ES may be limited.