Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001387150 | SCV001587701 | pathogenic | Actin accumulation myopathy | 2020-10-26 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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 ACTA1 protein function. This variant has been observed in individual(s) with autosomal dominant nemaline myopathy (PMID: 12921789). In at least one individual the variant was observed to be de novo. This variant is also known as p.Tyr279His in the literature. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with histidine at codon 281 of the ACTA1 protein (p.Tyr281His). The tyrosine residue is highly conserved and there is a moderate physicochemical difference between tyrosine and histidine. |