ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.1355-1G>C

dbSNP: rs747557404
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000596715 SCV000701271 pathogenic not provided 2016-06-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001072038 SCV001237381 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2023-12-25 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 10 of the CAPN3 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CAPN3 are known to be pathogenic (PMID: 10330340, 15689361). This variant is present in population databases (rs747557404, gnomAD 0.0009%). Disruption of this splice site has been observed in individuals with autosomal recessive CAPN3-related conditions (PMID: 16650086; Invitae). ClinVar contains an entry for this variant (Variation ID: 288426). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV000596715 SCV002018082 pathogenic not provided 2020-02-26 criteria provided, single submitter clinical testing
Baylor Genetics RCV003463772 SCV004213803 pathogenic Muscular dystrophy, limb-girdle, autosomal dominant 4 2023-12-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004701388 SCV005204310 pathogenic Autosomal recessive limb-girdle muscular dystrophy 2024-06-13 criteria provided, single submitter clinical testing Variant summary: CAPN3 c.1355-1G>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Three predict the variant abolishes a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 251400 control chromosomes. c.1355-1G>C has been reported in the literature in the homozygous and compound heterozygous states in individuals affected with Limb-Girdle Muscular Dystrophy or muscular dystrophy (e.g. Krahn_2006, Ten Dam_2019). These data indicate that the variant is likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 16650086, 30919934). ClinVar contains an entry for this variant (Variation ID: 288426). Based on the evidence outlined above, the variant was classified as pathogenic.
Natera, Inc. RCV001072038 SCV002085509 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2021-04-02 no assertion criteria provided clinical testing

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