Heart failure & cardiomyopathies
Underrepresentation of Diverse Ancestries Drives Uncertainty in Genetic Variants Found in Cardiomyopathy-Associated Genes
Authors' conclusion
Over the past 10 years, 7.3% of cardiomyopathy gene variants underwent a clinically meaningful change in pathogenicity assignment. Over 30% of downgrades from P/LP may be attributable to higher MAF in Non-Europeans than Europeans.
Study context
- Population
- Variants in 10 sarcomeric and 6 desmosomal cardiomyopathy-associated genes in ClinVar
- Participants
- 30,975 variants
- Outcome
- Clinically meaningful change in pathogenicity assignment (between P/LP, C/VUS and benign/likely benign)
- Follow-up
- 2011 to 2021
Methodological detailsClinVar and GnomAD data
- ClinVar and GnomAD data
Main finding
As reported in the abstract
Clinically meaningful change in pathogenicity assignment
Variants with clinically meaningful change
2,276
7.3%
Changes moving from P/LP or benign/likely benign to C/VUS
67%
Observational data: associations, not effects.
Further findings
Variants downgraded from P/LP: Minor allele frequency (MAF) >1 × 10 −4 in non-Europeans and <1 × 10 −4 in Europeans
- Proportion of P/LP downgrades
- 35%
Original publication
Underrepresentation of Diverse Ancestries Drives Uncertainty in Genetic Variants Found in Cardiomyopathy-Associated Genes. JACC Adv. Published 15 December 2023. doi:10.
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