ClinVar Miner

Submissions for variant NM_024426.6(WT1):c.1487A>G (p.Lys496Arg)

gnomAD frequency: 0.00001  dbSNP: rs760370132
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000812109 SCV000952413 uncertain significance Drash syndrome; Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome 2021-09-07 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with WT1-related conditions. This variant is present in population databases (rs760370132, ExAC 0.003%). This sequence change replaces lysine with arginine at codon 491 of the WT1 protein (p.Lys491Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine.
Fulgent Genetics, Fulgent Genetics RCV002495130 SCV002788583 uncertain significance Aniridia 1; Drash syndrome; Frasier syndrome; Meacham syndrome; Mesothelioma, malignant; Nephrotic syndrome, type 4; Wilms tumor 1; 11p partial monosomy syndrome 2021-10-22 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004001738 SCV004825382 uncertain significance Wilms tumor 1 2023-05-04 criteria provided, single submitter clinical testing This missense variant replaces lysine with arginine at codon 491 in the WT1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with WT1-related disorders in the literature. This variant has been identified in 2/251444 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GeneDx RCV004768679 SCV005377204 uncertain significance not provided 2023-11-14 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 32493750)

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