ClinVar

Description

The Y283C variant that is likely pathogenic was identified in the MYH7 gene. To our knowledge, this variant has not been published as a mutation or as a benign polymorphism. The Y283C 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 Y283C 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. Moreover, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense mutations in nearby residues (R281T, S291F), have been reported in association with DCM, 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. The variant is found in DCM-CRDM panel(s).