ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.1117T>C (p.Trp373Arg) (rs775453643)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000710091 SCV000255647 pathogenic not provided 2015-07-28 criteria provided, single submitter clinical testing Not found in the total gnomAD dataset, and the data is high quality. Assessment of experimental evidence suggests this variant results in abnormal protein function. Segregation with disease in affected individuals from a single family.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000710091 SCV000333339 uncertain significance not provided 2016-12-28 criteria provided, single submitter clinical testing
Invitae RCV000201159 SCV000645464 uncertain significance Limb-girdle muscular dystrophy, type 2A 2018-08-06 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with arginine at codon 373 of the CAPN3 protein (p.Trp373Arg). The tryptophan residue is moderately conserved and there is a moderate physicochemical difference between tryptophan and arginine. This variant is present in population databases (rs775453643, ExAC no frequency). This variant has been reported as homozygous in siblings affected with limb girdle muscular dystrophy, type 2A (PMID: 18337726). ClinVar contains an entry for this variant (Variation ID: 217145). Experimental studies have shown that this missense change affects the calcium-independent protease activity of the calpain 3 (p94) protein (PMID: 18258189). In summary, this variant has uncertain impact on CAPN3 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Counsyl RCV000201159 SCV000800735 uncertain significance Limb-girdle muscular dystrophy, type 2A 2017-10-10 criteria provided, single submitter clinical testing
Clinical Genetics Karolinska University Hospital,Karolinska University Hospital RCV000710091 SCV001450290 likely pathogenic not provided 2015-10-29 criteria provided, single submitter clinical testing

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