ClinVar

Description

Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. ACTC1 p.Ile177Val We consider this variant a variant of uncertain significance. The variant is novel. In silico analysis with PolyPhen-2 predicts the variant to be benign (HumVar score is 0.050). The isoleucine at codon 177 is completely conserved across species, as are neighboring amino acids. Other variants have been observed in association with disease at nearby codons (p.Ala172Thr (we classify as variant of uncertain significance), p.Tyr168Cys, p.Pro166Ala). This is a conservative amino acid substitution (Grantham score is 29). In total the variant has not been seen in ~6500 individuals from publicly available population datasets. There is no variation at codon 177 listed in the NHLBI Exome Sequencing Project dataset, which currently includes variant calls on ~6500 Caucasian and African American individuals (as of July 3rd, 2014). Of note, there are only three nonsynomous variants (all missense) in this gene in the ESP data set. 5 of 6500 individuals (0.077%) in this dataset have a nonsynomous variant in ACTC1. There is also no variation at this codon listed in dbSNP (as of July 5th, 2014).