Key result
Phenotype-directed cardiac gene panels yield ~3.6-fold more pathogenic variants than opportunistic exome screening.
Why the study?
Inherited arrhythmia syndromes and cardiomyopathies are genetically heterogeneous, and clinical exome sequencing for unrelated indications increasingly yields cardiovascular secondary findings under the ACMG SF v3.3 list, prompting comparison of phenotype-directed cardiac gene panel testing with opportunistically ascertained cardiovascular secondary findings.
Does phenotype-directed cardiac gene panel testing compare with or complement ACMG SF v3.3 screening in clinical exome sequencing for identifying pathogenic/likely pathogenic cardiovascular variants in a Korean cohort?
Cohort (n=328)
No
Does phenotype-directed cardiac gene panel testing compare with or complement ACMG SF v3.3 screening in clinical exome sequencing for identifying pathogenic/likely pathogenic cardiovascular variants in a Korean cohort?
Phenotype-directed cardiac gene panels and opportunistic ACMG SF v3.3 exome screening yield largely non-overlapping cardiovascular genetic diagnoses (20.0% vs 5.6% yield), demonstrating that the two approaches are complementary and highlighting the importance of population-specific variant interpretation.
Answers are grounded in this paper and cite their sources.
Supports targeted panels in suspected inherited cardiac disease; leaves open optimal integration with ACMG secondary findings screening.
Inherited arrhythmia syndromes and cardiomyopathies are genetically heterogeneous, and clinical exome sequencing (CES) for unrelated indications increasingly yields cardiovascular secondary findings (SFs) under the ACMG SF v3.3 list. We compared, at a single Korean centre, phenotype‐directed cardiac gene panel testing with opportunistically ascertained cardiovascular SFs. Forty patients with suspected inherited arrhythmia or cardiomyopathy underwent a 19‐gene arrhythmia or 173‐gene cardiomyopathy panel with AI‐assisted, manually reviewed variant classification; separately, 288 patients undergoing CES for unrelated indications were screened for ACMG SF v3.3 cardiovascular pathogenic/likely pathogenic variants. A phenotype‐concordant pathogenic/likely pathogenic variant was found in 8/40 patients (20.0%), including a recurrent KCNQ1 p.Arg231His variant in two unrelated infants and a MYBPC3 variant upgraded to pathogenic by co‐segregation in a mother‐son pair. Among the 288 exome‐sequenced patients, 17 reportable cardiovascular SFs occurred in 16 (5.6%), predominantly dilated cardiomyopathy ( n = 7, mostly TTN ) and familial hypercholesterolaemia ( n = 6, including a recurrent PCSK9 p.Glu32Lys variant in three patients). The two approaches sampled largely non‐overlapping gene categories and are complementary rather than competing; recurrent, population‐specific variants underscore the need for population‐informed interpretation and structured counselling in cardiovascular genetic diagnosis.
No takes yet. Share an insight, caveat, or question.
You et al. (2026) conducted a cohort in Inherited arrhythmia syndromes, cardiomyopathies, and cardiovascular disease (n=328). Phenotype-directed cardiac gene panel testing (19-gene arrhythmia or 173-gene cardiomyopathy panel) vs. Opportunistic ACMG SF v3.3 screening during clinical exome sequencing for unrelated indications was evaluated on Diagnostic yield of pathogenic or likely pathogenic cardiovascular variants. Phenotype-directed cardiac gene panel testing yielded pathogenic/likely pathogenic variants in 20.0% of suspected cases, while opportunistic ACMG SF v3.3 exome screening yielded 5.6%.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: