ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.656T>C (p.Val219Ala)

gnomAD frequency: 0.00006  dbSNP: rs373662682
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001922888 SCV002184900 uncertain significance not provided 2024-12-10 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 219 of the WFS1 protein (p.Val219Ala). This variant is present in population databases (rs373662682, gnomAD 0.02%). 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: 1411691). 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.
Fulgent Genetics, Fulgent Genetics RCV002484465 SCV002794099 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2024-01-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV002557652 SCV003627049 uncertain significance Inborn genetic diseases 2022-07-14 criteria provided, single submitter clinical testing The c.656T>C (p.V219A) alteration is located in exon 6 (coding exon 5) of the WFS1 gene. This alteration results from a T to C substitution at nucleotide position 656, causing the valine (V) at amino acid position 219 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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