ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.1319G>A (p.Arg440Gln)

gnomAD frequency: 0.00013  dbSNP: rs376107921
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000520664 SCV000255649 pathogenic not provided 2022-01-26 criteria provided, single submitter clinical testing The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). Experiments in patient-derived samples showed absence or significant reduction in CAPN3 protein level/activity in multiple patients (PMID: 15221789, 17994539, 18055493). In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic. Computational tools predict that this variant is damaging.
Eurofins Ntd Llc (ga) RCV000520664 SCV000331221 pathogenic not provided 2018-06-05 criteria provided, single submitter clinical testing
GeneDx RCV000520664 SCV000616670 pathogenic not provided 2023-07-14 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: 15221789, 18334579, 20694146, 18055493, 15689361, 17236769, 31589614, 21984748, 17994539, 15725583, 30564623, 32906206, 24077912, 32528171, 18854869, 33250842, 19048948, 25326637, 17526799, 33337384, 35169782)
Labcorp Genetics (formerly Invitae), Labcorp RCV000201096 SCV000645468 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2024-01-13 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 440 of the CAPN3 protein (p.Arg440Gln). This variant is present in population databases (rs376107921, gnomAD 0.02%). This missense change has been observed in individuals with autosomal recessive limb-girdle muscular dystrophy type 2A (PMID: 15221789, 18055493, 19048948, 20694146, 21984748, 25326637). ClinVar contains an entry for this variant (Variation ID: 217147). 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 not expected to disrupt CAPN3 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects CAPN3 function (PMID: 15221789, 18055493, 19048948, 20694146). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000762949 SCV000893373 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A; Muscular dystrophy, limb-girdle, autosomal dominant 4 2021-07-20 criteria provided, single submitter clinical testing
Baylor Genetics RCV000201096 SCV001529400 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2018-04-25 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Mayo Clinic Laboratories, Mayo Clinic RCV000520664 SCV001716214 pathogenic not provided 2020-08-28 criteria provided, single submitter clinical testing PS4, PM2, PM3, PM5, PP4
Kariminejad - Najmabadi Pathology & Genetics Center RCV001814105 SCV001755678 pathogenic Abnormality of the musculature 2021-07-10 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000520664 SCV002018044 pathogenic not provided 2023-09-27 criteria provided, single submitter clinical testing
Baylor Genetics RCV003474968 SCV004211507 pathogenic Muscular dystrophy, limb-girdle, autosomal dominant 4 2024-03-12 criteria provided, single submitter clinical testing
Counsyl RCV000201096 SCV000791421 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2017-05-10 no assertion criteria provided clinical testing
Natera, Inc. RCV000201096 SCV001454339 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2020-09-16 no assertion criteria provided clinical testing

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