ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.2251G>A (p.Glu751Lys)

dbSNP: rs147465252
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001562495 SCV001785269 uncertain significance not provided 2020-10-16 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); 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
Labcorp Genetics (formerly Invitae), Labcorp RCV001562495 SCV002157246 uncertain significance not provided 2023-12-14 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 751 of the WFS1 protein (p.Glu751Lys). This variant is present in population databases (rs147465252, 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: 1198372). 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 RCV002488381 SCV002786106 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2021-12-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002573175 SCV003541615 uncertain significance Inborn genetic diseases 2022-01-26 criteria provided, single submitter clinical testing The c.2251G>A (p.E751K) alteration is located in exon 8 (coding exon 7) of the WFS1 gene. This alteration results from a G to A substitution at nucleotide position 2251, causing the glutamic acid (E) at amino acid position 751 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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