ClinVar Miner

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

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000711016 SCV000333873 likely pathogenic not provided 2017-04-12 criteria provided, single submitter clinical testing
Invitae RCV000295812 SCV000645494 pathogenic Limb-girdle muscular dystrophy, type 2A 2020-07-13 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 observed in individuals affected with autosomal recessive limb-girdle muscular dystrophy (PMID: 205172126, 27066551, 26060040, 28403181). 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 and their clinical significance is uncertain. This variant disrupts the p.Arg769 amino acid residue in CAPN3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7720071, 12461690, 7795603, 7762565, 14645990). This suggests that this residue is clinically-significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Athena Diagnostics Inc RCV000711016 SCV000841334 likely pathogenic not provided 2020-02-25 criteria provided, single submitter clinical testing The frequency of this variant in the general population is consistent with pathogenicity. Found in at least one patient with expected phenotype for this gene. Predicted to have a damaging effect on the protein. One other pathogenic or likely pathogenic variant affects the same amino acid. In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic.
Genetics Laboratory, UDIAT-Centre Diagnòstic, Hospital Universitari Parc Tauli RCV001420333 SCV001622753 pathogenic See cases 2021-04-26 criteria provided, single submitter clinical testing PP5_strong;PM1_moderate;PM2_supporting;PM3_moderate;PM5_moderate;PP3_supporting;BP1_supporting
Counsyl RCV000295812 SCV000791434 likely pathogenic Limb-girdle muscular dystrophy, type 2A 2017-05-16 no assertion criteria provided clinical testing

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