ClinVar

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 314 of the ACTC1 protein (p.Arg314His). This variant is present in population databases (rs121912673, gnomAD 0.003%). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Arg314 amino acid residue in ACTC1. Other variant(s) that disrupt this residue have been observed in individuals with ACTC1-related conditions (PMID: 9563954, 23283745), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this missense change affects ACTC1 function (PMID: 19799913, 22590617, 24736382). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ACTC1 protein function. ClinVar contains an entry for this variant (Variation ID: 18323). This variant is also known as R312H. This missense change has been observed in individual(s) with clinical features of ACTC1-related conditions (PMID: 9563954, 34011823, 34495297, 34930662). It has also been observed to segregate with disease in related individuals.