ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.1795dup (p.Thr599fs) (rs80338803)

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Total submissions: 10
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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 Limb-girdle muscular dystrophy, type 2A 2016-03-18 criteria provided, single submitter reference population
Illumina Clinical Services Laboratory,Illumina RCV000019187 SCV000391025 pathogenic 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 Inc RCV000518261 SCV000612637 pathogenic not provided 2017-03-15 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000518261 SCV000701857 pathogenic not provided 2016-11-29 criteria provided, single submitter clinical testing
Invitae RCV000019187 SCV000951911 pathogenic Limb-girdle muscular dystrophy, type 2A 2019-09-15 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. This variant is present in population databases (rs745989418, ExAC 0.01%). This variant has been observed in several individuals affected with autosomal recessive limb-girdle muscular dystrophy (PMID: 9771675, 23677060, 26632398). ClinVar contains an entry for this variant (Variation ID: 17620). Loss-of-function variants in CAPN3 are known to be pathogenic (PMID: 10330340, 15689361). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000019187 SCV000039475 pathogenic Limb-girdle muscular dystrophy, type 2A 1998-11-01 no assertion criteria provided literature only
GeneReviews RCV000019187 SCV000040413 pathologic Limb-girdle muscular dystrophy, type 2A 2012-07-05 no assertion criteria provided curation Converted during submission to Pathogenic.
Department of Rehabilitation Medicine, Incheon St. Mary’s Hospital,College of Medicine, The Catholic University of Korea RCV000019187 SCV000882752 pathogenic 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 Limb-girdle muscular dystrophy, type 2A 2018-03-29 no assertion criteria provided clinical testing
Natera, Inc. RCV000019187 SCV001454346 pathogenic Limb-girdle muscular dystrophy, type 2A 2020-09-16 no assertion criteria provided clinical testing

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