Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000200584 | SCV000252559 | pathogenic | not provided | 2021-06-27 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate that this variant induces endoplasmic reticulum stress by affecting the protein folding and processing (De Franco et al., 2017); Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27535533, 28468959, 25211237, 27217304) |
| Equipe Genetique des Anomalies du Developpement, |
RCV000656404 | SCV000778412 | pathogenic | Wolfram-like syndrome | 2017-01-30 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000656404 | SCV002034834 | pathogenic | Wolfram-like syndrome | 2021-07-16 | criteria provided, single submitter | clinical testing | The WFS1 c.2425G>A (p.Glu809Lys) variant is a missense variant that has been reported in at least six individuals with Wolfram-like syndrome (Matsunaga et al. 2014; Chaussenot et al. 2015; Prochazkova et al. 2016; De Franco et al. 2017). The variant was noted to be found in a de novo state in three individuals for whom parental samples were available for testing (Prochazkova et al. 2016; De Franco et al. 2017). Affected individuals show clinical features of diabetes mellitus, optic atrophy, hearing loss, psychomotor delay, hypotonia and intellectual disability. Dysmorphic features are not common but have been noted in one patient (Prochazkova et al. 2016). The p.Glu809Lys variant is not found in the Genome Aggregation Database in either version 2.1.1 or version 3.1.1 in a region of good sequence coverage, so the variant is presumed to be rare. The Glu809 residue is located in the C-terminal region of the protein. Functional studies have shown that the p.Glu809Lys variant affects protein folding and has a dominant negative effect on the wild-type protein in HeLa and HEK293 cells, as measured by significantly increased endoplasmic reticulum stress response reporter activity in cells expressing the variant protein (De Franco et al. 2017; Batjargal et al. 2020). Based on the available evidence, the p.Glu809Lys variant is classified as pathogenic for Wolfram-like syndrome. |