Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000279141 | SCV000334251 | uncertain significance | not provided | 2015-08-14 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001859563 | SCV002109296 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2022-08-22 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 560 of the CAPN3 protein (p.Thr560Ala). This variant is present in population databases (rs146845466, gnomAD 0.005%). This missense change has been observed in individual(s) with autosomal recessive limb-girdle muscular dystrophy (PMID: 29970176). ClinVar contains an entry for this variant (Variation ID: 282679). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |
Revvity Omics, |
RCV000279141 | SCV003828913 | uncertain significance | not provided | 2022-07-20 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003230470 | SCV003928549 | uncertain significance | not specified | 2023-04-13 | criteria provided, single submitter | clinical testing | Variant summary: CAPN3 c.1678A>G (p.Thr560Ala) results in a non-conservative amino acid change located in the Peptidase C2, calpain, large subunit, domain III (IPR022682) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251408 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1678A>G has been reported in the literature in at least one compound heterozygous individual affected with Limb-Girdle Muscular Dystrophy (e.g. Fichna_2018). The variant was also found in other heterozygous individuals with suspected/confirmed diagnosis of Limb-Girdle Muscular Dystrophy (e.g. Nallamilli_2018, Meinke_2020). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters have assessed the variant since 2014: all have classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |