Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics | RCV000173976 | SCV000255655 | pathogenic | not provided | 2022-08-02 | criteria provided, single submitter | clinical testing | The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). In multiple individuals with LGMD, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic. Computational tools predict that this variant is damaging. |
| Eurofins Ntd Llc |
RCV000173976 | SCV000331924 | likely pathogenic | not provided | 2016-08-18 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000201107 | SCV001387850 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2024-01-12 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 493 of the CAPN3 protein (p.Arg493Trp). This variant is present in population databases (rs557164942, gnomAD 0.01%). This missense change has been observed in individuals with autosomal recessive limb-girdle muscular dystrophy (PMID: 10330340, 17236769, 18073330, 18334579, 25079074). ClinVar contains an entry for this variant (Variation ID: 193792). 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 expected to disrupt CAPN3 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
| Revvity Omics, |
RCV000173976 | SCV002025071 | likely pathogenic | not provided | 2021-04-27 | criteria provided, single submitter | clinical testing | |
| Neuberg Centre For Genomic Medicine, |
RCV000201107 | SCV004047724 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2A | criteria provided, single submitter | clinical testing | The CAPN3 c.1477C>T variant has been reported in individuals affected with Muscular dystrophy, limb-girdle, autosomal recessive 1 (Nilsson et. al., 2014; Benayoun et. al., 2008). The p.Arg493Trp variant is novel (not in any individuals) in 1000 Genomes and has allele frequency of 0.002832% in gnomAD database. This variant has been reported to the ClinVar database as Pathogenic/Likely Pathogenic. 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; PolyPhen2: Probably Damaging; Align-GVGD: Class C0). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. The amino acid Arg at position 493 is changed to a Trp changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Likely Pathogenic. | |
| Baylor Genetics | RCV003462275 | SCV004213766 | pathogenic | Muscular dystrophy, limb-girdle, autosomal dominant 4 | 2024-03-27 | criteria provided, single submitter | clinical testing | |
| Counsyl | RCV000201107 | SCV000791903 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2017-05-31 | no assertion criteria provided | clinical testing |