Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001343121 | SCV001537084 | uncertain significance | Drash syndrome; Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome | 2023-11-11 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 212 of the WT1 protein (p.Ile212Ser). 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: 1039612). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |
All of Us Research Program, |
RCV004005183 | SCV004819137 | uncertain significance | Wilms tumor 1 | 2023-06-08 | criteria provided, single submitter | clinical testing | This variant is located 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. |
Ambry Genetics | RCV004968077 | SCV005535971 | uncertain significance | Inborn genetic diseases | 2024-12-02 | criteria provided, single submitter | clinical testing | The p.I212S variant (also known as c.635T>G), located in coding exon 1 of the WT1 gene, results from a T to G substitution at nucleotide position 635. The isoleucine at codon 212 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |