ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.2149G>A (p.Glu717Lys)

gnomAD frequency: 0.00004  dbSNP: rs71532863
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000518926 SCV000617491 likely pathogenic not provided 2024-02-09 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 12955714, 21143470, 34746052, 36208030, 37510321)
Fulgent Genetics, Fulgent Genetics RCV002490902 SCV002780099 likely pathogenic Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2024-04-03 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000518926 SCV005777017 uncertain significance not provided 2024-12-10 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 717 of the WFS1 protein (p.Glu717Lys). This variant is present in population databases (rs71532863, gnomAD 0.01%). This missense change has been observed in individual(s) with autosomal recessive Wolfram syndrome and/or clinical features of Wolfram syndrome (PMID: 11244483, 12955714, 21143470, 37510321). ClinVar contains an entry for this variant (Variation ID: 449390). 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) has been performed 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.

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