ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.2305C>T (p.Arg769Trp) (rs868791726)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000711016 SCV000841334 likely pathogenic not provided 2017-09-08 criteria provided, single submitter clinical testing
Counsyl RCV000295812 SCV000791434 likely pathogenic Limb-girdle muscular dystrophy, type 2A 2017-05-16 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000711016 SCV000333873 likely pathogenic not provided 2017-04-12 criteria provided, single submitter clinical testing
Invitae RCV000295812 SCV000645494 likely pathogenic Limb-girdle muscular dystrophy, type 2A 2018-02-27 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 769 of the CAPN3 protein (p.Arg769Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the compound heterozygous in an individual affected with limb girdle-muscular dystrophy type 2A (PMID: 20517216). In addition, different missense substitutions at this codon (p.Arg769Gln, p.Arg769Pro) are reported to be deleterious in individuals with muscular dystrophy and eosinophilic myositis (PMID: 16607617, 7720071, 25987458). This indicates that the arginine residue is important for CAPN3 protein function. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. For these reasons, this variant has been classified as Likely Pathogenic.

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