Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001922339 | SCV002156927 | uncertain significance | not provided | 2022-11-16 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.Lys634 amino acid residue in WFS1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12181639). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on WFS1 protein function. ClinVar contains an entry for this variant (Variation ID: 1382930). This variant has not been reported in the literature in individuals affected with WFS1-related conditions. This variant is present in population databases (rs140213376, gnomAD 0.007%). This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 634 of the WFS1 protein (p.Lys634Gln). |
| Fulgent Genetics, |
RCV005038434 | SCV005667513 | uncertain significance | Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome | 2024-04-19 | criteria provided, single submitter | clinical testing |