Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000802073 | SCV000941887 | uncertain significance | Qualitative or quantitative defects of dysferlin | 2022-09-07 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 192 of the DYSF protein (p.Arg192His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of limb-girdle muscular dystrophy (PMID: 32400077). ClinVar contains an entry for this variant (Variation ID: 647545). 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 DYSF protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |