ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.1883C>T (p.Thr628Met)

gnomAD frequency: 0.00003  dbSNP: rs368236000
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001935060 SCV002172837 uncertain significance not provided 2023-11-10 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 628 of the WFS1 protein (p.Thr628Met). This variant is present in population databases (rs368236000, gnomAD 0.008%). 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: 1401302). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on WFS1 protein function. 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 RCV001935060 SCV002520235 uncertain significance not provided 2022-05-10 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
Fulgent Genetics, Fulgent Genetics RCV002506999 SCV002815538 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2021-12-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV003167067 SCV003871726 uncertain significance Inborn genetic diseases 2023-02-28 criteria provided, single submitter clinical testing The c.1883C>T (p.T628M) alteration is located in exon 8 (coding exon 7) of the WFS1 gene. This alteration results from a C to T substitution at nucleotide position 1883, causing the threonine (T) at amino acid position 628 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV004538599 SCV004116361 uncertain significance WFS1-related disorder 2022-09-14 criteria provided, single submitter clinical testing The WFS1 c.1883C>T variant is predicted to result in the amino acid substitution p.Thr628Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0070% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-6303405-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Breakthrough Genomics, Breakthrough Genomics RCV001935060 SCV005190022 uncertain significance not provided criteria provided, single submitter not provided

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