Variant Synonymizer: Platform to identify mutations defined in different ways is available now!
Over 2,000 gene–disease validation summaries are now available—no login required!
MYBPC3 encodes cardiac myosin-binding protein C, a sarcomeric protein well established in hypertrophic cardiomyopathy. Rare MYBPC3 variants have been reported in individuals meeting Task Force Criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC). In a single case report, a 26-year-old athlete with histologically confirmed ARVC carried NM_000256.3:c.3535G>A (p.Glu1179Lys), classified as a variant of unknown significance due to absence of known ARVC-associated mutations and lack of familial segregation (PMID:28843747). In a cohort of 137 unrelated ARVC probands screened for non-desmosomal genes, 6 (4%) harbored rare sarcomeric variants predicted to be damaging, including NM_000256.3:c.442G>A (p.Gly148Arg) in MYBPC3; these carriers were isolated cases without segregation data or ARVC-specific functional studies (PMID:29709087).
Inheritance follows an autosomal dominant pattern. No affected relatives with MYBPC3 variants have been documented to segregate with ARVC, and no experimental models have demonstrated a mechanistic link between MYBPC3 dysfunction and fibrofatty replacement of right ventricular myocardium. Given the small number of probands and absence of corroborating functional or segregation evidence, the association remains limited. Key Take-home: MYBPC3 testing for ARVC should be considered investigational pending further validation.
Gene–Disease AssociationLimited1 isolated proband with histologic ARVC and 1 additional sporadic case; no segregation or ARVC-specific functional data Genetic EvidenceLimitedMYBPC3 variants reported in 2 independent ARVC probands (c.3535G>A and c.442G>A) without family segregation Functional EvidenceLimitedNo experimental models or assays demonstrating MYBPC3 pathogenicity in ARVC context |