ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.2248G>A (p.Ala750Thr)

gnomAD frequency: 0.00009  dbSNP: rs201335980
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001305498 SCV001494835 uncertain significance not provided 2025-01-02 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 750 of the WFS1 protein (p.Ala750Thr). This variant is present in population databases (rs201335980, 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: 1008197). 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 RCV001305498 SCV001815179 uncertain significance not provided 2024-08-05 criteria provided, single submitter clinical testing 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
Fulgent Genetics, Fulgent Genetics RCV002486188 SCV002790609 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2024-05-20 criteria provided, single submitter clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV003128200 SCV003804234 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 rs201335980 in Wolfram's syndrome yet.

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