Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000597389 | SCV000700630 | likely pathogenic | not provided | 2017-11-07 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000597389 | SCV001500662 | pathogenic | not provided | 2020-11-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000673077 | SCV001581101 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2024-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 214 of the CAPN3 protein (p.Gly214Ser). This variant is present in population databases (rs369784333, gnomAD 0.02%). This missense change has been observed in individual(s) with autosomal recessive limb-girdle muscular dystrophy (PMID: 19556129, 25135358, 30919934). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 496915). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CAPN3 protein function with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV000597389 | SCV001817263 | uncertain significance | not provided | 2020-06-25 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 10330340, 30919934, 31589614, 19556129, 25135358, 30564623) |
Revvity Omics, |
RCV000597389 | SCV002016920 | pathogenic | not provided | 2021-06-21 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002509457 | SCV002819558 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy | 2022-12-15 | criteria provided, single submitter | clinical testing | Variant summary: CAPN3 c.640G>A (p.Gly214Ser) results in a non-conservative amino acid change located in the Peptidase C2, calpain, catalytic domain 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 8.7e-05 in 251464 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in CAPN3 causing Limb-Girdle Muscular Dystrophy, Autosomal Recessive (8.7e-05 vs 0.0032), allowing no conclusion about variant significance. c.640G>A has been reported in the literature in multiple individuals affected with Limb-Girdle Muscular Dystrophy, Autosomal Recessive. These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (Pathogenic/likely pathogenic n=5, VUS n=1). Based on the evidence outlined above, the variant was classified as pathogenic. |
Baylor Genetics | RCV003471951 | SCV004211539 | pathogenic | Muscular dystrophy, limb-girdle, autosomal dominant 4 | 2023-10-08 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000673077 | SCV000798245 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2018-03-08 | no assertion criteria provided | clinical testing |