ClinVar

Description

The S1335L variant in the MYH7 gene has not been published as a , nor has it been reported as a benign polymorphism to our knowledge. The S1335L 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 S1335L 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 is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Missense variants in nearby residues (A1332T, R1337Q, R1344W) have been reported in the Human Gene Mutation Database in association with cardiomyopathy (Stenson et al., 2014), supporting the functional importance of this region of the protein. The S1335L variant is a strong candidate for a disease-causing variant which may be related to the lower extremity weakness reported in this individual. However, the possibility it may be a rare benign variant cannot be excluded.