Key result
Expanded pediatric cardiac genetic panels linked to fewer actionable variants despite testing more genes.
Why the study?
Genetic testing for pediatric arrhythmia and cardiomyopathy disorders is evolving, with unclear trends in variant classification over time.
Observational (n=583)
Effect estimate: r = 0.97
p-value: p=<0.001
The expansion of genetic testing panels in pediatric cardiology over time has led to an increased identification of variants of uncertain significance, emphasizing the importance of specialized genetic counseling.
Expanded panels linked to fewer actionable variants in pediatric cases; leaves open optimal panel design for clinical utility.
Genetic testing for cardiac disorders continues to change. Our objective was to assess trends in variant classification in pediatric arrhythmia and cardiomyopathy. We conducted a retrospective review of patients tested for genetic arrhythmia and cardiomyopathy disorders from 2006-2017. Variants were classified by CLIA laboratories. Trends were assessed by the Spearman correlation. There were 914 variants in 583 patients from 337 families. The total number of tests ordered increased over time, accelerating after 2012. There was a strong positive correlation between the average number of genes tested per panel and year of testing (r = .97, p < .001) and a weak correlation between the year and a decrease in the percentage of clinically actionable variants (r = -.20, p = .005). By 2011, VUS represented >50% of variants reported on panels. Over 12 years, 203 genes were interrogated; one or more variants were reported in 91 of 203 genes (45%). 32% of patients had at least one clinically actionable variant; 28% had at least one VUS. Reclassification is an important long-term issue, with 21.5% variants changing clinical interpretation. We observed an increase over time in three areas: total number of tests ordered, average number of genes/panel, and percentage of VUS. Providers may need to interpret results from 90 + genes, and ongoing education is critical. Due to their specific training in test result interpretation, we recommend the inclusion of a genetic counselor in pediatric electrophysiology and cardiomyopathy teams.
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Cherny et al. (2020) conducted an observational in Pediatric arrhythmia and cardiomyopathy (n=583). Genetic testing was evaluated on Trends in variant classification and genes tested per panel over time (r = 0.97, p=<0.001). Genetic testing for pediatric arrhythmia and cardiomyopathy from 2006-2017 showed a strong increase in genes tested per panel (r=0.97, p<0.001) and a decrease in clinically actionable variants.
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