Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000158538 | SCV000208473 | uncertain significance | not provided | 2014-04-30 | criteria provided, single submitter | clinical testing | p.Ala820Val (GCC>GTC): c.2459 C>T in exon 22 of the MYH7 gene (NM_000257.2). The A820V variant has not been published as a mutation or as a benign polymorphism to our knowledge. The A820V variant was not observed in approximately 6,500 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 A820V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, this substitution occurs at a position that is not conserved across species. Nevertheless, in silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, missense mutations in nearby residues (I818N, R819Q, M822T, M822V) have been reported in association with cardiomyopathy, supporting the functional importance of this region of the protein. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in CARDIOMYOPATHY panel(s). |