Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Revvity Omics, |
RCV003146957 | SCV003829658 | uncertain significance | not provided | 2019-10-09 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003738374 | SCV004522749 | likely pathogenic | Qualitative or quantitative defects of dysferlin | 2023-09-08 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 2441128). This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 1008 of the DYSF protein (p.Asp1008His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with limb-girdle muscular dystrophy (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. 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. 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. |