ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.1342C>G (p.Arg448Gly)

dbSNP: rs776043976
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Total submissions: 4
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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 (formerly Invitae), Labcorp 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, 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

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