ClinVar Miner

Submissions for variant NM_006005.3(WFS1):c.1264G>A (p.Ala422Thr)

gnomAD frequency: 0.00004  dbSNP: rs773280611
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001556041 SCV001777550 uncertain significance not provided 2024-12-11 criteria provided, single submitter clinical testing In silico analysis indicates 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 RCV002495887 SCV002785610 uncertain significance Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome 2024-03-20 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001556041 SCV003295696 uncertain significance not provided 2023-05-22 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 1193594). This variant has not been reported in the literature in individuals affected with WFS1-related conditions. This variant is present in population databases (rs773280611, gnomAD 0.01%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 422 of the WFS1 protein (p.Ala422Thr).
Ambry Genetics RCV004968210 SCV005528654 uncertain significance Inborn genetic diseases 2024-10-20 criteria provided, single submitter clinical testing The c.1264G>A (p.A422T) 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 1264, causing the alanine (A) at amino acid position 422 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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