ClinVar Miner

Submissions for variant NM_024426.6(WT1):c.70C>T (p.Arg24Cys) (rs878855086)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000229861 SCV000290755 uncertain significance Drash syndrome; Frasier syndrome; Wilms tumor 1; Wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome 2020-06-06 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 19 of the WT1 protein (p.Arg19Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with WT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 241484). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0. The cysteine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
St. Jude Clinical Genomics Lab, St. Jude Children's Research Hospital RCV001526809 SCV001737448 uncertain significance Wilms tumor 1 2021-05-27 criteria provided, single submitter clinical testing The WT1 c.55C>T (p.Arg19Cys) missense change is absent in gnomAD v2.1.1 (PM2_Supporting; https://gnomad.broadinstitute.org/). Four of six in silico tools predict a benign effect of this variant on protein function (BP4), but to our knowledge these predictions have not been confirmed by functional assays. To our knowledge, this variant has not been reported in individuals with WT1-related conditions. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: PM2_Supporting, BP4.

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