ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.1063C>T (p.Arg355Trp)

gnomAD frequency: 0.00001  dbSNP: rs749099493
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000711013 SCV000331918 pathogenic not provided 2017-06-21 criteria provided, single submitter clinical testing
Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota RCV000389096 SCV000840444 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2017-05-25 criteria provided, single submitter clinical testing
Athena Diagnostics RCV000711013 SCV000841330 pathogenic not provided 2018-01-26 criteria provided, single submitter clinical testing
Invitae RCV000389096 SCV001200165 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2024-01-04 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 355 of the CAPN3 protein (p.Arg355Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with autosomal recessive limb-girdle muscular dystrophy (PMID: 15689361, 17236769, 19364062, 23821418, 29970176). ClinVar contains an entry for this variant (Variation ID: 281254). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CAPN3 protein function with a positive predictive value of 80%. This variant disrupts the p.Arg355 amino acid residue in CAPN3. Other variant(s) that disrupt this residue have been observed in individuals with CAPN3-related conditions (PMID: 16650086, 28403181), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV000711013 SCV002025069 likely pathogenic not provided 2019-04-03 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000711013 SCV002063411 pathogenic not provided 2021-12-01 criteria provided, single submitter clinical testing
Baylor Genetics RCV003463741 SCV004213771 pathogenic Muscular dystrophy, limb-girdle, autosomal dominant 4 2024-03-20 criteria provided, single submitter clinical testing
Counsyl RCV000389096 SCV000793223 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2017-08-04 no assertion criteria provided clinical testing
Natera, Inc. RCV000389096 SCV001454334 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2020-09-16 no assertion criteria provided clinical testing

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