ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.1195T>G (p.Trp399Gly)

gnomAD frequency: 0.00011  dbSNP: rs767561828
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000727080 SCV000252525 uncertain significance not provided 2023-08-24 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 to our knowledge
Eurofins Ntd Llc (ga) RCV000727080 SCV000705470 uncertain significance not provided 2017-01-12 criteria provided, single submitter clinical testing
Invitae RCV000727080 SCV002314811 uncertain significance not provided 2024-01-25 criteria provided, single submitter clinical testing This sequence change replaces tryptophan, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 399 of the WFS1 protein (p.Trp399Gly). This variant is present in population databases (rs767561828, gnomAD 0.02%). 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: 215386). 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 80%. 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, Fulgent Genetics RCV002500615 SCV002782708 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2022-04-21 criteria provided, single submitter clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002509294 SCV002817354 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 rs767561828 in Wolfram's syndrome yet.
PreventionGenetics, part of Exact Sciences RCV004530179 SCV004119888 uncertain significance WFS1-related disorder 2023-03-24 criteria provided, single submitter clinical testing The WFS1 c.1195T>G variant is predicted to result in the amino acid substitution p.Trp399Gly. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.024% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-6302717-T-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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