Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000669159 | SCV000793879 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2017-09-12 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000669159 | SCV001420516 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2025-01-11 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 448 of the CAPN3 protein (p.Arg448Gly). This variant is present in population databases (rs776043976, gnomAD 0.003%). This missense change has been observed in individuals with autosomal recessive limb-girdle muscular dystrophy (PMID: 10330340, 16650086, 18055493; internal data). ClinVar contains an entry for this variant (Variation ID: 553662). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt CAPN3 protein function with a positive predictive value of 80%. This variant disrupts the p.Arg448 amino acid residue in CAPN3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10330340, 17236769, 18854869, 20635405, 25135358). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV003472111 | SCV004211501 | pathogenic | Muscular dystrophy, limb-girdle, autosomal dominant 4 | 2024-03-28 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV005010657 | SCV005635686 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2A; Muscular dystrophy, limb-girdle, autosomal dominant 4 | 2024-05-01 | criteria provided, single submitter | clinical testing |