ClinVar Miner

Submissions for variant NM_024426.6(WT1):c.691C>T (p.Pro231Ser)

gnomAD frequency: 0.00001  dbSNP: rs766425764
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000433791 SCV000535245 uncertain significance not provided 2017-01-11 criteria provided, single submitter clinical testing The P226S variant in the WT1 gene has not, to our knowledge, been published in the literature as pathogenic or benign. This variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Proline and Serine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. The P226S variant occurs at a position that is conserved in mammals and is not located in a known functional domain. In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, we consider P226S to be a variant of uncertain significance.
Fulgent Genetics, Fulgent Genetics RCV002502586 SCV002814337 uncertain significance Aniridia 1; Drash syndrome; Frasier syndrome; Meacham syndrome; Mesothelioma, malignant; Nephrotic syndrome, type 4; Wilms tumor 1; 11p partial monosomy syndrome 2021-07-25 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002525485 SCV003449439 uncertain significance Drash syndrome; Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome 2023-07-17 criteria provided, single submitter clinical testing 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. This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 226 of the WT1 protein (p.Pro226Ser). This variant is present in population databases (rs766425764, gnomAD 0.006%). 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: 392045). 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.

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