Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000200051 | SCV000252530 | uncertain significance | not provided | 2022-03-04 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign in association with a WFS1-related disorder to our knowledge; This variant is associated with the following publications: (PMID: 31589614, 10521293, 33046911) |
Personalized Diabetes Medicine Program, |
RCV001174422 | SCV001337560 | uncertain significance | Monogenic diabetes | 2018-03-27 | criteria provided, single submitter | research | ACMG criteria: PP3 (10 predictors, REVEL=0.939), PM1 (transmembrane domain PMID:10521293)=VUS |
Invitae | RCV000200051 | SCV002198142 | uncertain significance | not provided | 2024-01-19 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 537 of the WFS1 protein (p.Cys537Tyr). This variant is present in population databases (rs199910987, gnomAD 0.1%). This missense change has been observed in individual(s) with clinical features of WFS1-related conditions (PMID: 33046911). ClinVar contains an entry for this variant (Variation ID: 215390). 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 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. |
Ambry Genetics | RCV002517280 | SCV003735385 | uncertain significance | Inborn genetic diseases | 2022-08-17 | criteria provided, single submitter | clinical testing | Unlikely to be causative of autosomal dominant WFS1-related Wolfram syndrome (AD) Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |