ClinVar

Description

This missense variant replaces arginine with glutamine at codon 502 in the Ig-like domain C3 of the MYBPC3 protein. Computational prediction tools and conservation analyses suggest that this variant may have a deleterious impact on protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant. This variant has been reported in over 20 individuals affected with hypertrophic cardiomyopathy (PMID: 20433692, 22112859, 9562578, 16566405, 18403758, 18533079, 20433692, 22267749, 22857948, 27600940, 28193612). It has been shown that this variant segregates with hypertrophic cardiomyopathy in multiple unrelated families (PMID: 20433692, 22112859). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). A different missense variant occurring at the same codon, p.Arg502Trp, is known to be disease-causing (Clinvar variation ID 42540), indicating that arginine at this position is important for protein function. Based on available evidence, this variant is classified as Pathogenic.