ClinVar

Description

The A259E variant of uncertain significance has been identified in the MYH7 gene. The A259Evariant has been previously reported in one individual with HCM, however no clinical information wasprovided on this patient (Waldmuller et al., 2008). The A259E variant was not observed inapproximately 6,500 individuals of European and African American ancestry in the NHLBI ExomeSequencing Project, indicating it is not a common benign variant in these populations. A259E is anon-conservative amino acid substitution, which is likely to impact secondary protein structure asthese residues differ in polarity, charge, size and/or other properties. This substitution occurs at aposition that is conserved across species and in silico analysis predicts this variant is probablydamaging to the protein structure/function. Although missense variants in nearby residues (F252S,G256E, I263M, I263T) have been reported in the Human Gene Mutation Database in association withHCM (Stenson et al., 2014), the full significance of these variants is unknown. Additionally, despitethe fact that this variant has been published in association with HCM, family history information andsegregation data was not provided. Furthermore, no functional studies for the A259E variant havebeen performed.