ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.1504A>G (p.Ile502Val)

gnomAD frequency: 0.00004  dbSNP: rs755433765
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000541575 SCV000645473 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2A 2022-08-09 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 502 of the CAPN3 protein (p.Ile502Val). This variant is present in population databases (rs755433765, gnomAD 0.04%). 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: 468643). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant disrupts the p.Ile502 amino acid residue in CAPN3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10330340, 26810512, 30919934; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000541575 SCV002564431 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2A 2022-05-13 criteria provided, single submitter clinical testing A Heterozygous missense variation in exon 11 of CAPN3 gene that result in the amino acid substitution of valine for Isoleucine at codon 502 was detected. Observed variant was previously reported in patient affected with limb-girdle muscular dystrophy This variant has not been reported in the 1000 genomes, and has a MAF of 0.003% in the gnomAD database. The in silico prediction of variant is damaging by PolyPhen-2 (HumDiv). In summary, the variant meets our criteria to be classified as a variant of uncertain significance.
Natera, Inc. RCV000541575 SCV002085518 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2A 2019-10-28 no assertion criteria provided clinical testing

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