Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001755690 | SCV002005304 | uncertain significance | not provided | 2024-12-02 | criteria provided, single submitter | clinical testing | Reported in an individual with hearing loss in published literature (PMID: 38400873); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 38400873) |
Labcorp Genetics |
RCV001755690 | SCV002172994 | uncertain significance | not provided | 2024-06-11 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 146 of the WFS1 protein (p.Arg146His). This variant is present in population databases (rs34446752, gnomAD 0.01%). 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: 1319042). 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) has been performed at Invitae 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. |
Prevention |
RCV004528533 | SCV004107239 | uncertain significance | WFS1-related disorder | 2022-12-21 | criteria provided, single submitter | clinical testing | The WFS1 c.437G>A variant is predicted to result in the amino acid substitution p.Arg146His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.010% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-6290835-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Ce |
RCV001755690 | SCV004147629 | uncertain significance | not provided | 2022-07-01 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004681249 | SCV005174961 | uncertain significance | Inborn genetic diseases | 2024-05-29 | criteria provided, single submitter | clinical testing | The c.437G>A (p.R146H) alteration is located in exon 4 (coding exon 3) of the WFS1 gene. This alteration results from a G to A substitution at nucleotide position 437, causing the arginine (R) at amino acid position 146 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV005038312 | SCV005664677 | uncertain significance | Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome | 2024-06-21 | criteria provided, single submitter | clinical testing |