Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000152700 | SCV000202079 | uncertain significance | not specified | 2013-06-12 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Pathogenic. The Glu824Lys i n WFS1 has not been reported in affected individuals, but has been identified in 0.01% (1/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/). Although thi s variant has been seen in this cohort, it should be noted that for diseases wit h clinical variability, reduced penetrance, or recessive inheritance, pathogenic variants may be present at a low frequency in the general population. Computati onal analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyP hen2, and SIFT) do not provide strong support for or against an impact to the pr otein. In summary, additional information is needed to fully assess the clinical significance of this variant. |
Eurofins Ntd Llc |
RCV000726782 | SCV000702984 | uncertain significance | not provided | 2016-11-02 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000726782 | SCV001812758 | uncertain significance | not provided | 2020-07-21 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31363008) |
Labcorp Genetics |
RCV000726782 | SCV002184091 | uncertain significance | not provided | 2024-03-21 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 824 of the WFS1 protein (p.Glu824Lys). This variant is present in population databases (rs367547063, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of Wolfram/Wolfram-like syndrome (PMID: 31363008). ClinVar contains an entry for this variant (Variation ID: 166612). 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. |
Fulgent Genetics, |
RCV002498721 | SCV002775703 | uncertain significance | Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome | 2022-03-25 | criteria provided, single submitter | clinical testing | |
Clinical Genomics, |
RCV003147360 | SCV003804398 | 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 rs367547063 in Wolfram's syndrome yet. |