ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.1318C>T (p.Arg440Trp)

gnomAD frequency: 0.00001  dbSNP: rs777323132
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000725372 SCV000336423 pathogenic not provided 2018-04-12 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000269452 SCV000645467 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2024-03-16 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 440 of the CAPN3 protein (p.Arg440Trp). This variant is present in population databases (rs777323132, gnomAD 0.005%). This missense change has been observed in individuals with autosomal recessive limb-girdle muscular dystrophy (PMID: 9150160, 11525884, 22926650, 26060040). ClinVar contains an entry for this variant (Variation ID: 283991). 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%. This variant disrupts the p.Arg440 amino acid residue in CAPN3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15221789, 18055493, 19048948, 20694146, 21984748, 25326637). 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.
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000269452 SCV000778588 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2018-04-16 criteria provided, single submitter research
Counsyl RCV000269452 SCV000795542 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2017-11-09 criteria provided, single submitter clinical testing
Kariminejad - Najmabadi Pathology & Genetics Center RCV001814145 SCV001755540 pathogenic Abnormality of the musculature 2021-07-10 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000725372 SCV003822466 likely pathogenic not provided 2022-01-03 criteria provided, single submitter clinical testing
GeneDx RCV000725372 SCV005874583 likely pathogenic not provided 2024-08-29 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31589614, 18055493, 22926650, 11371436, 11525884, 9150160, 26060040, 38374194, 31788660)
Natera, Inc. RCV000269452 SCV002085504 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2020-08-18 no assertion criteria provided clinical testing
Baylor Genetics RCV003475903 SCV004211513 pathogenic Muscular dystrophy, limb-girdle, autosomal dominant 4 2023-10-22 flagged submission clinical testing

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