ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.956C>T (p.Pro319Leu)

gnomAD frequency: 0.00001  dbSNP: rs121434547
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000417420 SCV000338158 likely pathogenic not provided 2017-09-20 criteria provided, single submitter clinical testing
GeneDx RCV000417420 SCV000515988 likely pathogenic not provided 2024-02-01 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); 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: 34426522, 9642272, 15689361, 16141003, 11371436, 34602496, 30919934, 17562833, 31937337, 9150160, 18073330, 36374152, 30056071)
Labcorp Genetics (formerly Invitae), Labcorp RCV000019183 SCV000823087 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2023-12-29 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 319 of the CAPN3 protein (p.Pro319Leu). This variant is present in population databases (rs121434547, gnomAD 0.004%). This missense change has been observed in individuals with autosomal recessive limb-girdle muscular dystrophy (PMID: 9150160, 30056071, 30919934, 34602496). ClinVar contains an entry for this variant (Variation ID: 17617). 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 95%. Experimental studies have shown that this missense change affects CAPN3 function (PMID: 9642272). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV000417420 SCV002025070 likely pathogenic not provided 2021-04-23 criteria provided, single submitter clinical testing
Baylor Genetics RCV003473107 SCV004211542 pathogenic Muscular dystrophy, limb-girdle, autosomal dominant 4 2024-03-25 criteria provided, single submitter clinical testing
OMIM RCV000019183 SCV000039471 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 1997-05-01 no assertion criteria provided literature only
Counsyl RCV000019183 SCV000795213 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2019-04-17 no assertion criteria provided clinical testing

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