Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001035334 | SCV001198659 | uncertain significance | Drash syndrome; Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome | 2024-11-05 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 40 of the WT1 protein (p.Trp40Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with WT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 834611). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on WT1 protein function. 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. |
| Sema4, |
RCV002258087 | SCV002530517 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-18 | criteria provided, single submitter | curation | |
| All of Us Research Program, |
RCV004004690 | SCV004825377 | uncertain significance | Wilms tumor 1 | 2023-05-04 | criteria provided, single submitter | clinical testing | This missense variant replaces tryptophan with glycine at codon 40 in the WT1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with WT1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |