ClinVar

Description

This mutation is denoted c.886 T>A at the cDNA level or p.Tyr296Asn (Y296N) at the protein level. Although Tyr296Asn has not been reported previously as a disease-causing mutation to our knowledge, Tyr296Asn results in a non-conservative amino acid substitution of Tyrosine residue 296, a phosphotyrosine site that is a highly conserved position in the alpha-actin gene across several species. Another missense mutation affecting an adjacent codon, Ala297Ser (aka A297S), has been reported in association with HCM (Mogensen J et al., 1999). Mogensen et al. reported that this residue is localized at the actin surface close to a possible myosin-binding site, further supporting the functional importance of this region of the protein. In addition, the NHLBI ESP Exome Variant Server reports Tyr296Asn was not observed in approximately 5,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. Therefore, the presence of this mutation indicates that an individual can be at increased risk to develop HCM. However, other genetic and environmental factors influence disease expression and severity, and some mutation carriers may never become symptomatic.The variant is found in ACTC1 panel(s).