ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.956C>T (p.Pro319Leu) (rs121434547)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000019183 SCV000795213 likely pathogenic Limb-girdle muscular dystrophy, type 2A 2017-11-06 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000417420 SCV000338158 likely pathogenic not provided 2017-09-20 criteria provided, single submitter clinical testing
GeneDx RCV000417420 SCV000515988 pathogenic not provided 2015-03-10 criteria provided, single submitter clinical testing The P319L variant in the CAPN3 gene has been reported previously in the compound heterozygous state inmultiple affected family members and one unrelated individual with limb-girdle muscular dystrophy type 2A(Richard et al., 1997; Piluso et al., 2005). The P319L variant was not observed in approximately 6,500individuals of European and African American ancestry in the NHLBI Exome Sequencing Project; however,data from ethnically-matched control individuals were not available to assess for a population-specific benignvariant. The P319L substitution is a semi-conservative amino acid substitution, which may impact secondaryprotein structure as these residues differ in some properties. This substitution occurs at a position that isconserved through mammals. In addition, missense variants in nearby residues (V320F, Y322H) have beenreported in the Human Gene Mutation Database in association with limb-girdle muscular dystrophy (Stenson etal., 2014), supporting the functional importance of this region of the protein. We interpret P319L as a pathogenic variant.
Invitae RCV000019183 SCV000823087 uncertain significance Limb-girdle muscular dystrophy, type 2A 2018-03-06 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 319 of the CAPN3 protein (p.Pro319Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs121434547, ExAC 0.006%). This variant has been reported in combination with another CAPN3 variant in individuals affected with limb girdle muscular dystrophy type 2A (PMID: 9150160, 16141003 ). ClinVar contains an entry for this variant (Variation ID: 17617). Experimental studies have shown that this missense change impairs the function of the CAPN3 protein (PMID: 9642272). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
OMIM RCV000019183 SCV000039471 pathogenic Limb-girdle muscular dystrophy, type 2A 1997-05-01 no assertion criteria provided literature only

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