ClinVar

Description

Variant summary: MYL3 c.235G>A (p.Val79Ile) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 251470 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.235G>A has been reported in the literature as segregating with disease in at least one family, in which one heterozygous individual was diagnosed with asymptomatic hypertrophic cardiomyopathy (HCM) and 3 additional heterozygotes displayed borderline HCM; unaffected heterozygous carriers in the family were under the age of 30, suggesting this variant may cause late-onset and clinically silent disease (Andersen_2012). Therefore, this report does not provide unequivocal conclusions about association of the variant with Hypertrophic Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five ClinVar submitters (evaluation after 2014) have cited the variant, and all laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.