Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| 3billion | RCV002283617 | SCV002572547 | uncertain significance | Wolfram syndrome 1 | 2022-09-01 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.98; 3Cnet: 0.97). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with WFS1-related disorder (PMID: 19042979). The variant has been reported to co-segregate with the disease in at least one similarly affected relative/individual in the same family or similarly affected unrelated family (PMID: 19042979). However, since the evidence of pathogenicity is insufficient at this time, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. |
| Labcorp Genetics |
RCV003096372 | SCV003525596 | pathogenic | not provided | 2022-09-23 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 664 of the WFS1 protein (p.Leu664Arg). This missense change has been observed in individual(s) with autosomal recessive Wolfram syndrome (PMID: 19042979). It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as 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. |