Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000819470 | SCV000960133 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2023-11-07 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 483 of the CAPN3 protein (p.Ala483Asp). This variant is present in population databases (rs781723572, gnomAD 0.002%). This missense change has been observed in individuals with clinical features of autosomal recessive limb-girdle muscular dystrophy (PMID: 15689361, 16141003; Invitae). ClinVar contains an entry for this variant (Variation ID: 661943). 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 CAPN3 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |