ClinVar Miner

Submissions for variant NM_024426.6(WT1):c.1124G>T (p.Arg375Leu)

dbSNP: rs554416372
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000799894 SCV000939578 uncertain significance Drash syndrome; Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome 2023-12-07 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 370 of the WT1 protein (p.Arg370Leu). This variant is present in population databases (rs554416372, gnomAD 0.01%). This missense change has been observed in individual(s) with Wilms' tumor and gonadal dysgenesis, along with another variant (IVS6-1G>T) in the same WT1 gene (PMID: 21384108). ClinVar contains an entry for this variant (Variation ID: 645745). 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 disruptive. 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.
GeneDx RCV004702427 SCV005202006 uncertain significance not provided 2024-03-04 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in an individual with prostate cancer (PMID: 34579513); Identified in an individual with Denys-Drash syndrome who was also heterozygous for a WT1 canonical splice site variant, phase unknown (PMID: 21384108); This variant is associated with the following publications: (PMID: 34579513, 17361230, 21384108)

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.