Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV000191145 | SCV000245554 | likely pathogenic | Wolfram syndrome 1 | 2013-10-22 | criteria provided, single submitter | clinical testing | Likely pathogenicity based on finding it once in our laboratory in trans with a pathogenic variant [F883fs] in a 38-year-old female with Asperger, ataxia, optic atrophy, progressive vision impairment, spastic bladder, chronic fatigue, irregular menses |
| Invitae | RCV001852540 | SCV002281703 | likely pathogenic | not provided | 2021-08-06 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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 expected to disrupt WFS1 protein function. ClinVar contains an entry for this variant (Variation ID: 209206). This missense change has been observed in individual(s) with clinical features of autosomal recessive Wolfram syndrome (PMID: 24088041). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with arginine at codon 755 of the WFS1 protein (p.Cys755Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. |
| Clinical Genomics, |
RCV000191145 | SCV003804235 | likely 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 rs797045075 in Wolfram's syndrome yet. |