Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001922151 | SCV002149198 | uncertain significance | not provided | 2023-11-20 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 205 of the WFS1 protein (p.Gly205Ser). This variant is present in population databases (rs770713329, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with WFS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1382171). 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 with a negative predictive value of 95%. 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, |
RCV002503473 | SCV002781821 | uncertain significance | Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome | 2021-12-26 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001922151 | SCV003921382 | uncertain significance | not provided | 2022-10-27 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Prevention |
RCV004529034 | SCV004108925 | uncertain significance | WFS1-related disorder | 2022-11-28 | criteria provided, single submitter | clinical testing | The WFS1 c.613G>A variant is predicted to result in the amino acid substitution p.Gly205Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.035% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-6293076-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |