ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.1795dup (p.Thr599fs)

dbSNP: rs80338803
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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center RCV000019187 SCV000267238 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2016-03-18 criteria provided, single submitter reference population
Illumina Laboratory Services, Illumina RCV000019187 SCV000391025 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2017-04-27 criteria provided, single submitter clinical testing The CAPN3 c.1795dupA (p.Thr599AsnfsTer33) variant results in a frameshift and is predicted to result in premature truncation of the protein. The p.Thr599AsnfsTer33 variant has been reported in three studies in which it is found in a total of six patients including in three in a compound heterozygous state and three in a homozygous state (Kawai et al. 1998; Chae et al. 2001; Matsuura et al. 2013). In one study, the homozygous individual was shown to be born to consanguineous asymptomatic parents who were found to be heterozygous for the variant (Matsuura et al. 2013). The p.Thr599AsnfsTer33 variant was absent from 94 controls and is reported at a frequency of 0.00012 in the East Asian population of the Exome Aggregation Consortium. This is based on one allele in a region of good coverage so the variant is presumed to be rare. Based on the evidence and the potential impact of frameshift variants, the p.Thr599AsnfsTer33 variant is classified as pathogenic for calpainopathy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Athena Diagnostics RCV000518261 SCV000612637 pathogenic not provided 2017-03-15 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000518261 SCV000701857 pathogenic not provided 2016-11-29 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000019187 SCV000951911 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2024-03-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr599Asnfs*33) in the CAPN3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CAPN3 are known to be pathogenic (PMID: 10330340, 15689361). This variant is present in population databases (rs745989418, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with autosomal recessive limb-girdle muscular dystrophy (PMID: 9771675, 23677060, 26632398). ClinVar contains an entry for this variant (Variation ID: 17620). For these reasons, this variant has been classified as Pathogenic.
Kariminejad - Najmabadi Pathology & Genetics Center RCV001814001 SCV001755443 pathogenic Abnormality of the musculature 2021-07-10 criteria provided, single submitter clinical testing
Baylor Genetics RCV003473109 SCV004211540 pathogenic Muscular dystrophy, limb-girdle, autosomal dominant 4 2023-12-30 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005007875 SCV005637800 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A; Muscular dystrophy, limb-girdle, autosomal dominant 4 2024-04-10 criteria provided, single submitter clinical testing
OMIM RCV000019187 SCV000039475 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 1998-11-01 no assertion criteria provided literature only
GeneReviews RCV000019187 SCV000040413 not provided Autosomal recessive limb-girdle muscular dystrophy type 2A no assertion provided literature only Pathogenic variant most likely the result of a founder effect followed by genetic isolation in a population in Japan [Kawai et al 1998, Chae et al 2001].
Department of Rehabilitation Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea RCV000019187 SCV000882752 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2019-02-11 no assertion criteria provided research The proband has another variant, NM_000070.2: c.1118G>A (p.Trp373*).
Counsyl RCV000019187 SCV001132348 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2018-03-29 no assertion criteria provided clinical testing
Natera, Inc. RCV000019187 SCV001454346 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2020-09-16 no assertion criteria provided clinical testing

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