Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000152666 | SCV000202025 | uncertain significance | not specified | 2017-09-29 | criteria provided, single submitter | clinical testing | The p.Lys239Arg variant in WFS1 has not been previously reported in any other fa milies with hearing loss or in any individuals with WFS1-related disorders. This variant has also been identified in 3/33580 Latino chromosomes by the Genome Ag gregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs727503747) ; however its frequency is not high enough to rule out a pathogenic role. Comput ational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Lys239Arg variant is uncertain. ACMG/AMP Criteria applied: PM2; BP4 (Ri chards 2015). |
| Fulgent Genetics, |
RCV000765774 | SCV000897163 | uncertain significance | Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome | 2021-09-15 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001857525 | SCV002191045 | uncertain significance | not provided | 2022-12-10 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs727503747, gnomAD 0.009%). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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: 166574). This variant has not been reported in the literature in individuals affected with WFS1-related conditions. This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 239 of the WFS1 protein (p.Lys239Arg). |
| Clinical Genomics, |
RCV002509249 | SCV002773882 | uncertain risk allele | 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 rs727503747 in Wolfram's syndrome yet. | |
| Ambry Genetics | RCV002516065 | SCV003760425 | uncertain significance | Inborn genetic diseases | 2022-01-12 | criteria provided, single submitter | clinical testing | The c.716A>G (p.K239R) alteration is located in exon 7 (coding exon 6) of the WFS1 gene. This alteration results from a A to G substitution at nucleotide position 716, causing the lysine (K) at amino acid position 239 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |