Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV001195275 | SCV001365584 | uncertain significance | not specified | 2019-06-07 | criteria provided, single submitter | clinical testing | The p.Ile767Leu variant in WFS1 has not been previously reported in individuals with hearing loss, Wolfram syndrome, or Wolfram-like disorder, but has been identified in 0.007% (8/110278) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: none. |
Labcorp Genetics |
RCV001863085 | SCV002290380 | uncertain significance | not provided | 2024-10-08 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 767 of the WFS1 protein (p.Ile767Leu). This variant is present in population databases (rs779199009, gnomAD 0.007%). 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: 929934). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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. |
Gene |
RCV001863085 | SCV002559739 | uncertain significance | not provided | 2023-06-07 | 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 |
Clinical Genomics, |
RCV003128198 | SCV003804233 | uncertain 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 rs779199009 in Wolfram's syndrome yet. | |
Fulgent Genetics, |
RCV005040005 | SCV005667556 | uncertain significance | Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome | 2024-05-07 | criteria provided, single submitter | clinical testing |