Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000314946 | SCV000344161 | uncertain significance | not provided | 2016-07-27 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000686362 | SCV000813878 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2022-02-10 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 203 of the CAPN3 protein (p.Ala203Val). This variant is present in population databases (rs763719290, gnomAD 0.006%). 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: 289751). 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: "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. |
Ambry Genetics | RCV001267485 | SCV001445666 | uncertain significance | Inborn genetic diseases | 2019-06-18 | criteria provided, single submitter | clinical testing | |
3billion | RCV000686362 | SCV003841629 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2023-02-23 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). The variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.93; 3Cnet: 0.81). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with CAPN3 related disorder (PMID: 35169782). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. |