ArticleAmerican journal of human genetics2023
The penetrance of rare variants in cardiomyopathy-associated genes: A cross-sectional approach to estimating penetrance for secondary findings.
Article in American journal of human genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- Complication management in hypertrophic cardiomyopathy.Heart failure reviews · 2026Review
- Automated patch clamp data improve variant classification and penetrance stratification for SCN5A-Brugada syndrome.European heart journal · 2026Article
- Article
- Variant Site-Specific Natural History of Titin-Induced Cardiomyopathy: An International Multicenter Registry.Circulation. Genomic and precision medicine · 2026Article
- Genetic Testing Yield for Dilated Cardiomyopathy in a Single Lithuanian Center.Diagnostics (Basel, Switzerland) · 2026Article
- Genetic counselling implementation in dilated cardiomyopathy.European heart journal · 2026Review
- Pediatric Genomic Medicine-rapid progress, but not too fast: American Pediatric Society's 2026 John Howland Award Lecture.Pediatric research · 2026Article
- Epidemiology of non-ischaemic dilated cardiomyopathy.Nature reviews. Cardiology · 2026Review
- Population Prevalence, Penetrance, and Mortality for Genetically Confirmed MODY.The Journal of clinical endocrinology and metabolism · 2026Article
- Evaluation of Women With Peripartum or Dilated Cardiomyopathy and Their First-Degree Relatives: The DCM Precision Medicine Study.Circulation. Genomic and precision medicine · 2026Observational
- Structural Evaluation ofCirculation. Genomic and precision medicine · 2026Article
- Semi-automated genomic newborn screening highlights complexities in reporting.NPJ genomic medicine · 2026Article
- Over-Representation of TTN Truncating Variants in a Finnish Cohort of Patients With Axial Myopathy.European journal of neurology · 2026Article
- A TNNT2 variant in a sporadic case of dilated cardiomyopathy: a case report and review.Frontiers in cardiovascular medicine · 2026Article
- Familial left ventricular noncompaction cardiomyopathy associated with the p.Asp461AsnOpen life sciences · 2026Article
- What Should a Clinical Cardiologist Know About Cardiogenetics?Journal of the American Heart Association · 2025Review
- Prime editing corrects the dilated cardiomyopathy causing RBM20-P633L-mutation in human cardiomyocytes.Molecular therapy. Nucleic acids · 2025Article
- A combined genomic arrhythmia propensity score delineates cumulative risk.Cell reports. Medicine · 2025Article
- Redefining the Genetic Architecture of Hypertrophic Cardiomyopathy: Role of Intermediate-Effect Variants.Circulation · 2025Article
- Genetic risk in telomere biology disorders: it adds up.The Journal of clinical investigation · 2025Article
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Authors and funding
23 authors.
Funding
Abstract
Understanding the penetrance of pathogenic variants identified as secondary findings (SFs) is of paramount importance with the growing availability of genetic testing. We estimated penetrance through large-scale analyses of individuals referred for diagnostic sequencing for hypertrophic cardiomyopathy (HCM; 10,400 affected individuals, 1,332 variants) and dilated cardiomyopathy (DCM; 2,564 affected individuals, 663 variants), using a cross-sectional approach comparing allele frequencies against reference populations (293,226 participants from UK Biobank and gnomAD). We generated updated prevalence estimates for HCM (1:543) and DCM (1:220). In aggregate, the penetrance by late adulthood of rare, pathogenic variants (23% for HCM, 35% for DCM) and likely pathogenic variants (7% for HCM, 10% for DCM) was substantial for dominant cardiomyopathy (CM). Penetrance was significantly higher for variant subgroups annotated as loss of function or ultra-rare and for males compared to females for variants in HCM-associated genes. We estimated variant-specific penetrance for 316 recurrent variants most likely to be identified as SFs (found in 51% of HCM- and 17% of DCM-affected individuals). 49 variants were observed at least ten times (14% of affected individuals) in HCM-associated genes. Median penetrance was 14.6% (±14.4% SD). We explore estimates of penetrance by age, sex, and ancestry and simulate the impact of including future cohorts. This dataset reports penetrance of individual variants at scale and will inform the management of individuals undergoing genetic screening for SFs. While most variants had low penetrance and the costs and harms of screening are unclear, some individuals with highly penetrant variants may benefit from SFs.
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