Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000669701 | SCV000794478 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2B | 2017-09-27 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002531236 | SCV003251734 | uncertain significance | Qualitative or quantitative defects of dysferlin | 2022-07-22 | 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 1005 of the DYSF protein (p.Arg1005Trp). This variant is present in population databases (rs778316824, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of dysferlinopathy (PMID: 25133958). This variant is also known as Arg1023Trp. ClinVar contains an entry for this variant (Variation ID: 554130). 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 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. |