ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.245C>T (p.Pro82Leu) (rs886042478)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000489536 SCV000334423 pathogenic not provided 2018-07-11 criteria provided, single submitter clinical testing
GeneDx RCV000489536 SCV000577327 pathogenic not provided 2017-04-04 criteria provided, single submitter clinical testing The P82L pathogenic variant in the CAPN3 gene has been previously reported, both in the homozygous and compound heterozygous state, in individuals with LGMD2A (de Paula et al., 2002; Vainzof et al., 2003; Milic et al., 2005; Hermanova et al., 2006). The P82L variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals, and missense variants in nearby residues (D77N, E79Q, F80L, S86F, L87V) have been reported in the Human Gene Mutation Database in association with limb-girdle muscular dystrophy (Stenson et al., 2014), supporting the functional importance of this region of the protein.
Athena Diagnostics Inc RCV000489536 SCV000612642 pathogenic not provided 2016-10-04 criteria provided, single submitter clinical testing
Invitae RCV000311426 SCV000830891 pathogenic Limb-girdle muscular dystrophy, type 2A 2020-10-27 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 82 of the CAPN3 protein (p.Pro82Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be homozygous or in combination with another CAPN3 variant in many individuals affected with limb-girdle muscular dystrophy (PMID: 12461690, 12890817, 15221789, 15351423, 16100770, 16141003, 16372320, 17157502, 20635405, 25135358, 26886200, 27447704). ClinVar contains an entry for this variant (Variation ID: 282783). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000489536 SCV001246423 pathogenic not provided 2018-08-01 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000489536 SCV001446731 likely pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Counsyl RCV000311426 SCV000788754 likely pathogenic Limb-girdle muscular dystrophy, type 2A 2016-12-15 no assertion criteria provided clinical testing

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