Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000158153 | SCV000208088 | likely pathogenic | not provided | 2014-03-15 | criteria provided, single submitter | clinical testing | p.Pro775Arg (CCT>CGT): c.2324 C>G in exon 24 of the MYBPC3 gene (NM_000256.3) The P775R variant that is likely pathogenic was identified in the MYBPC3 gene. It has not been published as a mutation or as a benign polymorphism to our knowledge. The P775R variant was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The P775R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense mutations in nearby residues (D770N, V771A, V771M, A774T) have been reported in association with HCM, supporting the functional importance of this region of the protein.Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded. Mutations in the MYBPC3 gene have been reported in 20%-30% of patients with autosomal dominant familial hypertrophic cardiomyopathy, and have been reported less frequently in patients with autosomal dominant familial dilated cardiomyopathy (Cirino A et al., 2011;Hershberger R et al., 2009). The variant is found in HCM panel(s). |