Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000152676 | SCV000202040 | uncertain significance | not specified | 2014-07-16 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The Gly466Ser varia nt in WFS1 has not been previously reported in individuals with hearing loss and was absent from large population studies. Computational prediction tools and co nservation analyses suggest that the Gly466Ser variant may not impact the protei n, though this information is not predictive enough to rule out pathogenicity. I n summary, while the clinical significance of the Gly466Ser variant is uncertain , the computational and conservation data suggest that it is more likely to be b enign. |
| ARUP Laboratories, |
RCV000756932 | SCV000884921 | uncertain significance | not provided | 2017-11-21 | criteria provided, single submitter | clinical testing | The p.Gly466Ser variant (rs727503750) has not been reported in the medical literature, nor has it been previously identified in our laboratory. The p.Gly466Ser variant is also listed in the Genome Aggregation Database (gnomAD) browser with an overall allele frequency of 0.00082% (identified in 2 out of 244,534 chromosomes), and is classified as a variant of uncertain significance in ClinVar (Variant ID: 166589). The glycine at codon 466 is moderately conserved considering 12 species (Alamut software v2.10.0), and computational analyses predict conflicting effects of this variant on protein structure/function (SIFT: tolerated, PolyPhen2: benign, MutationTaster: disease causing). Based on the available information, the clinical significance of the p.Gly466Ser variant cannot be determined with certainty. |
| Fulgent Genetics, |
RCV000765781 | SCV000897170 | uncertain significance | Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000756932 | SCV002152146 | uncertain significance | not provided | 2021-08-19 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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: 166589). This variant has not been reported in the literature in individuals affected with WFS1-related conditions. This sequence change replaces glycine with serine at codon 466 of the WFS1 protein (p.Gly466Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. |
| Clinical Genomics, |
RCV003126547 | SCV003801363 | uncertain significance | Wolfram syndrome 1 | criteria provided, single submitter | research | Potent mutations in WFS1 gene are associated with Wolfram's syndrome, an autosomal recessive condition, which cause diabetes mellitus, diabetes insipidus, deafness and optic atrophy. However no sufficient evidence is found to ascertain the role of this particular variant rs727503750 in Wolfram's syndrome yet. |