ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.1756G>A (p.Ala586Thr)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV003325164 SCV004031014 uncertain significance not provided 2023-08-11 criteria provided, single submitter clinical testing Reported in the heterozygous state in a patient with cognitive impairment and abnormal brain imaging in published literature (Chen et al., 2023); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 11244483, 36816038)
Labcorp Genetics (formerly Invitae), Labcorp RCV003325164 SCV004278747 uncertain significance not provided 2024-09-01 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 586 of the WFS1 protein (p.Ala586Thr). This variant is present in population databases (rs143084511, gnomAD 0.01%). 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: 2577827). 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 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 RCV005047530 SCV005672328 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2024-02-01 criteria provided, single submitter clinical testing

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