ClinVar

Description

The Met165Val variant in the MYH7 gene has not been reported as a pathogenic variant or as a benign polymorphism to our knowledge. Met165Val results in a conservative amino acid substitution of one non-polar amino acid for another at a position that is conserved across species. In silico analysis predicts Met165Val is damaging to the protein structure/function. Variants in nearby residues (Tyr162Cys, Tyr162His, Tyr177Ile) have been reported in association with cardiomyopathy, further supporting the functional importance of this region of the protein. Furthermore, Met165Val was not present in the 1000 Genomes database, and the NHLBI ESP Exome Variant Server reports Met165Val was not observed in approximately 6000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.