Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003052656 | SCV003444701 | uncertain significance | not provided | 2023-02-01 | 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 61 of the WFS1 protein (p.Ala61Thr). 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. 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. This variant has not been reported in the literature in individuals affected with WFS1-related conditions. |
Fulgent Genetics, |
RCV005034614 | SCV005664671 | uncertain significance | Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome | 2024-06-17 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV004738660 | SCV005351592 | uncertain significance | WFS1-related disorder | 2024-06-07 | no assertion criteria provided | clinical testing | The WFS1 c.181G>A variant is predicted to result in the amino acid substitution p.Ala61Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0042% of alleles in individuals of South Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |