ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.1637G>A (p.Arg546His)

gnomAD frequency: 0.00001  dbSNP: rs762091599
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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) RCV000279969 SCV000337537 uncertain significance not provided 2015-12-04 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000347867 SCV000391021 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2A 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina RCV000389952 SCV000391022 uncertain significance Limb-Girdle Muscular Dystrophy, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000347867 SCV000645475 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2A 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 546 of the CAPN3 protein (p.Arg546His). This variant is present in population databases (rs762091599, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CAPN3-related conditions. ClinVar contains an entry for this variant (Variation ID: 284783). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV002502121 SCV002781883 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2A; Muscular dystrophy, limb-girdle, autosomal dominant 4 2021-09-04 criteria provided, single submitter clinical testing
Natera, Inc. RCV000347867 SCV001460838 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2A 2020-03-17 no assertion criteria provided clinical testing

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