ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.686T>C (p.Met229Thr)

gnomAD frequency: 0.00001  dbSNP: rs774525063
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001965346 SCV002211412 uncertain significance not provided 2024-03-11 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 229 of the WFS1 protein (p.Met229Thr). This variant is present in population databases (rs774525063, gnomAD 0.009%). This missense change has been observed in individual(s) with diabetes (PMID: 30663027). ClinVar contains an entry for this variant (Variation ID: 1439615). 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 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.
Fulgent Genetics, Fulgent Genetics RCV002484702 SCV002791332 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2022-02-24 criteria provided, single submitter clinical testing
GeneDx RCV001965346 SCV005325597 uncertain significance not provided 2023-10-03 criteria provided, single submitter clinical testing Reported in a patient with pre-gestational diabetes in published literature (PMID: 30663027); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30663027)

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