ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs121907909
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000471023 SCV000545507 pathogenic Drash syndrome; Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome 2023-09-13 criteria provided, single submitter clinical testing This variant is also known as p.Arg390*. This sequence change creates a premature translational stop signal (p.Arg458*) in 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 (PMID: 15150775). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with Wilms tumor and Denys-Drash syndrome (PMID: 9108089, 10571943, 12471221, 15150775, 21508141, 21851196, 23117548, 23515051). ClinVar contains an entry for this variant (Variation ID: 3494). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000521800 SCV000617561 pathogenic not provided 2024-02-27 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Published functional studies demonstrate a damaging effect: reduced DNA binding affinity (PMID: 35610319); Not observed at significant frequency in large population cohorts (gnomAD); Also known as c.1387C>T; p.(R463*); This variant is associated with the following publications: (PMID: 15150775, 23117548, 12471221, 27701157, 8388765, 1317572, 21508141, 23515051, 19205749, 21851196, 9108089, 25818337, 10571943, 29869118, 30712057, 31278746, 34031707, 34308104, 25525159, 35610319, 34845858)
Athena Diagnostics RCV000521800 SCV001880670 pathogenic not provided 2020-12-01 criteria provided, single submitter clinical testing This variant is expected to result in the loss of a functional protein. This variant was not reported in large, multi-ethnic, general populations (http://gnomad.broadinstitute.org). This variant appears to occur de novo in multiple individuals with clinical features associated with this gene.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002293974 SCV002587315 pathogenic Focal segmental glomerulosclerosis 2022-02-24 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002504738 SCV002800415 pathogenic Aniridia 1; Drash syndrome; Frasier syndrome; Meacham syndrome; Mesothelioma, malignant; Nephrotic syndrome, type 4; Wilms tumor 1; 11p partial monosomy syndrome 2021-07-24 criteria provided, single submitter clinical testing
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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