Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics Inc | RCV000518215 | SCV000613197 | uncertain significance | not specified | 2016-10-05 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001239622 | SCV001412508 | likely pathogenic | Qualitative or quantitative defects of dysferlin | 2023-11-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1046 of the DYSF protein (p.Arg1046Cys). This variant is present in population databases (rs752810646, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with DYSF-related conditions. ClinVar contains an entry for this variant (Variation ID: 447285). 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 DYSF protein function with a positive predictive value of 95%. This variant disrupts the p.Arg1046 amino acid residue in DYSF. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11468312, 18853459, 25591676, 27647186). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Revvity Omics, |
RCV003144306 | SCV003831284 | uncertain significance | not provided | 2019-07-12 | criteria provided, single submitter | clinical testing | |
Gene |
RCV003144306 | SCV003837186 | uncertain significance | not provided | 2023-03-04 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 24438169) |
Natera, |
RCV001834664 | SCV002082264 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2B | 2019-10-28 | no assertion criteria provided | clinical testing |