ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.889A>G (p.Met297Val)

dbSNP: rs1553878254
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000611113 SCV000713713 uncertain significance not specified 2017-10-24 criteria provided, single submitter clinical testing The p.Met297Val variant in WFS1 has not been previously reported in individuals with hearing loss or WFS1-related disorders, or in large population studies. Com putational prediction tools and conservation analysis suggest that the p.Met297V al variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the p.Met297Val variant is uncertain. ACMG/AMP Criteria applied: PM2, BP4 (Richards 2015).
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002509467 SCV002774916 uncertain significance 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 rs1553878254 in Wolfram's syndrome yet.
Fulgent Genetics, Fulgent Genetics RCV002491238 SCV002789025 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2024-03-22 criteria provided, single submitter clinical testing
GeneDx RCV002508236 SCV002817792 uncertain significance not provided 2024-05-01 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV002508236 SCV005832286 uncertain significance not provided 2025-01-19 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 297 of the WFS1 protein (p.Met297Val). 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: 506178). 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.

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