Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000379326 | SCV000331206 | pathogenic | not provided | 2016-01-15 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001244501 | SCV001417727 | pathogenic | Qualitative or quantitative defects of dysferlin | 2022-08-09 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly426 amino acid residue in DYSF. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15477515). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. ClinVar contains an entry for this variant (Variation ID: 281067). This variant is also known as NM_001130987.1:c.1372G>A p.G458R. This missense change has been observed in individual(s) with DYSF-related myopathy (PMID: 18853459, 19309282, 32400077, 32528171). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 426 of the DYSF protein (p.Gly426Arg). |