ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.2299A>C (p.Ile767Leu)

gnomAD frequency: 0.00004  dbSNP: rs779199009
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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 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 (formerly Invitae), Labcorp 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.
GeneDx 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, Uppaluri K&H Personalized Medicine Clinic 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, 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

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