ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.1378G>A (p.Ala460Thr)

gnomAD frequency: 0.00002  dbSNP: rs767998582
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002040252 SCV002289818 uncertain significance not provided 2024-01-25 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 460 of the WFS1 protein (p.Ala460Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 1499525). 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 RCV002486621 SCV002781449 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2022-03-26 criteria provided, single submitter clinical testing

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