Total submissions: 3
| 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 | |
| Invitae | RCV000669159 | SCV001420516 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2023-05-10 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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. 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. ClinVar contains an entry for this variant (Variation ID: 553662). This missense change has been observed in individuals with autosomal recessive limb-girdle muscular dystrophy (PMID: 10330340, 16650086, 18055493; Invitae). This variant is present in population databases (rs776043976, gnomAD 0.003%). 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). |
| Baylor Genetics | RCV003472111 | SCV004211501 | pathogenic | Muscular dystrophy, limb-girdle, autosomal dominant 4 | 2023-10-30 | criteria provided, single submitter | clinical testing |