ClinVar

Description

p.Ala323Val (GCT>GTT): c.968 C>T in exon 6 of the ACTC1 gene (NM_005159.4). The A323V mutation in the ACTC1 gene has been reported in one patient with HCM (Maron B et al., 2012). Maron et al. identified A323V in an 18 year old male with HCM who harbored another mutation in the MYBPC3 gene and had a family history of sudden cardiac death. This study did not observed this mutation in 300 control chromosomes. Additionally, A323V was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The A323V mutation is a non-conservative amino acid substitution as these residues differ in polarity, charge, size and/or other properties and is more likely to impact secondary structure. The A323 residue is highly conserved across species. Mutations in nearby residues (R314H, A333P) have been reported in association with cardiomyopathy further supporting the functional importance of this region of the protein. In summary, A323V in the ACTC1 gene is interpreted as a disease-causing mutation. The variant is found in HCM panel(s).