P233: A family-based approach to cascade genetic testing in a pediatric cancer clinic: Challenges in test uptake and utility

Of these 8 new findings, 2 were repeat expansions, 1 was a mitochondrial variant, and 5 were coding variants, with 2 of these coding variants reclassified from variant of uncertain significance (VUS) to likely pathogenic.None of the 3 coding variants newly identified in GS were in GC rich or repetitive regions.Two out of these 3 coding variants were in genes described in published literature before initiation of ES.The other of those three coding variants resided in a gene that was associated with a relevant phenotype in a paper released the same month as the patient's ES report.Conclusion: These findings emphasize the technical differences between ES and GS, particularly the ability of certain GS data pipelines to detect repeat expansions on top of structural and mitochondrial variants usually missed by ES approaches.They also highlight the value of gene discovery over time.However, the additional yield of GS following ES appears to be less than 10%.Challenges in non-coding variant interpretation and establishing gene-disease associations remain significant barriers to improving the diagnostic yield of GS.