ClinVar

Description

The MYBPC3 c.3330+5G>C variant is predicted to interfere with splicing. This variant has been reported in multiple individuals with hypertrophic cardiomyopathy (Watkins et al. 1995. PubMed ID: 7493025; Table S7 - Alfares et al. 2015. PubMed ID: 25611685). In one family, the variant segregated in seven individuals with hypertrophic cardiomyopathy over three generations and was absent in eight unaffected individuals (Watkins et al. 1995. PubMed ID: 7493025). Of note, one unaffected individual was positive for this variant (Watkins et al. 1995. PubMed ID: 7493025). Splicing studies indicate this variant leads to exon skipping, which results in premature protein truncation (Watkins et al. 1995. PubMed ID: 7493025). This variant has been interpreted as pathogenic in the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/42706/). Additionally, different variants affecting the same nucleotide (c.3330+5G>A and c.3330+5G>T) have been reported in individuals with hypertrophic cardiomyopathy (Table S7 - Alfares et al. 2015. PubMed ID: 25611685; Table S1 - Wang et al. 2014. PubMed ID: 25132132). This variant is reported in 0.031% of alleles in individuals of African descent in gnomAD. This variant is interpreted as pathogenic.