Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000498432 | SCV000590071 | uncertain significance | not provided | 2017-06-05 | criteria provided, single submitter | clinical testing | The V536E variant in the WFS1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The V536E variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The V536E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret V536E as a variant of uncertain significance. |
| Clinical Genomics, |
RCV003126759 | SCV003801413 | likely risk allele | Wolfram syndrome 1 | criteria provided, single submitter | research | Potent mutations in WFS1 gene are associated with Wolfram's syndrome, an autosomal recessive condition, which cause diabetes mellitus, diabetes insipidus, deafness and optic atrophy. However no sufficient evidence is found to ascertain the role of this particular variant rs1553878625 in Wolfram's syndrome yet. | |
| Labcorp Genetics |
RCV000498432 | SCV005706041 | uncertain significance | not provided | 2024-05-31 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 536 of the WFS1 protein (p.Val536Glu). This variant is not present in population databases (gnomAD no frequency). 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: 432354). 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. 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. |