Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000369442 | SCV000344162 | uncertain significance | not provided | 2016-07-27 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000700400 | SCV000829153 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2022-02-10 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 250 of the CAPN3 protein (p.Lys250Arg). This variant is present in population databases (rs779939785, 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: 289752). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 | RCV001267486 | SCV001445667 | uncertain significance | Inborn genetic diseases | 2019-06-18 | criteria provided, single submitter | clinical testing | |
3billion | RCV000700400 | SCV003841412 | 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: 0.40; 3Cnet: 0.76). 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. |