Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001757328 | SCV002007469 | uncertain significance | not provided | 2019-07-09 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Fulgent Genetics, |
RCV002477994 | SCV002782156 | uncertain significance | Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome | 2021-12-13 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV001757328 | SCV003823765 | uncertain significance | not provided | 2021-08-02 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001757328 | SCV004344811 | uncertain significance | not provided | 2023-04-21 | 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. 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 WFS1 protein function. ClinVar contains an entry for this variant (Variation ID: 1315881). This variant has not been reported in the literature in individuals affected with WFS1-related conditions. This variant is present in population databases (rs377102310, gnomAD 0.01%). This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 764 of the WFS1 protein (p.Pro764Ala). |