Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000685030 | SCV000812501 | pathogenic | Actin accumulation myopathy | 2018-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with glycine at codon 140 of the ACTA1 protein (p.Ala140Gly). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with myofibrillar myopathy (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). The observation of one or more missense substitutions at this codon (p.Ala140Pro and p.Ala140Asp) in affected individuals suggests that this may be a clinically significant residue (PMID: 12921789, 19562689). For these reasons, this variant has been classified as Pathogenic. |