Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002005192 | SCV002264569 | uncertain significance | not provided | 2023-11-01 | 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 772 of the WFS1 protein (p.Arg772Cys). This variant is present in population databases (rs149540655, gnomAD 0.2%). This missense change has been observed in individual(s) with type 1 diabetes (PMID: 31264968). ClinVar contains an entry for this variant (Variation ID: 1473197). 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 WFS1 protein function with a positive predictive value of 80%. 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. |
| Fulgent Genetics, |
RCV002479629 | SCV002794297 | uncertain significance | Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome | 2022-03-11 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002573371 | SCV003711822 | uncertain significance | Inborn genetic diseases | 2022-05-10 | criteria provided, single submitter | clinical testing | Unlikely to be causative of AD WSF1-related Wolfram syndrome and AD WFS1-related low frequency sensorineural hearing loss. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |