ClinVar Miner

Submissions for variant NM_024426.6(WT1):c.1387C>T (p.Arg463Ter) (rs121907909)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000471023 SCV000545507 pathogenic Drash syndrome; Frasier syndrome; Wilms tumor 1; Wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome 2017-11-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 458 (p.Arg458*) of the WT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in WT1 are known to be pathogenic. This particular variant has been reported in the literature in several individuals affected with Wilms tumor with or without genitourinary anomalies (PMID: 9108089, 15150775, 21508141, 23515051, 23117548, 12471221). It has also been observed in individuals affected with Denys-Drash syndrome (PMID: 21851196) and Frasier syndrome (PMID: 10571943). In some cases, the variant was shown to be de novo (PMID: 10571943, 23515051, 21851196). This variant is also known as p.Arg390* in the literature. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000521800 SCV000617561 pathogenic not provided 2018-11-05 criteria provided, single submitter clinical testing This variant is denoted WT1 c.1372C>T at the cDNA level and p.Arg458Ter (R458X) at the proteinlevel. The substitution creates a nonsense variant, which changes an Arginine to a premature stop codon (CGA>TGA),and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNAdecay. This variant, also reported as R390X and 1168C>T, has been reported in patients with Wilms tumor andgenitourinary abnormalities (Little 1992, Schumacher 1997, Kohsaka 1999, Bockenhauer 2009, Köhler 2011, Yue 2011,Lipska 2013, Lehnhardt 2015) and is considered pathogenic
OMIM RCV000003666 SCV000023829 pathogenic Wilms tumor 1 1997-04-15 no assertion criteria provided literature only
OMIM RCV000030877 SCV000023841 pathogenic Frasier syndrome 1999-01-01 no assertion criteria provided literature only

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