ClinVar Miner

Submissions for variant NM_024426.6(WT1):c.1562C>T (p.Ala521Val)

gnomAD frequency: 0.00001  dbSNP: rs749266841
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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 RCV000824506 SCV000965406 uncertain significance Drash syndrome; Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome 2022-10-24 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt WT1 protein function. ClinVar contains an entry for this variant (Variation ID: 666088). This variant has not been reported in the literature in individuals affected with WT1-related conditions. This variant is present in population databases (rs749266841, gnomAD 0.01%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 516 of the WT1 protein (p.Ala516Val).
Fulgent Genetics, Fulgent Genetics RCV002507448 SCV002815611 uncertain significance Aniridia 1; Drash syndrome; Frasier syndrome; Meacham syndrome; Mesothelioma, malignant; Nephrotic syndrome, type 4; Wilms tumor 1; 11p partial monosomy syndrome 2022-01-29 criteria provided, single submitter clinical testing
GeneDx RCV003235415 SCV003933583 uncertain significance not provided 2022-12-13 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
All of Us Research Program, National Institutes of Health RCV004002865 SCV004822974 uncertain significance Wilms tumor 1 2024-01-11 criteria provided, single submitter clinical testing This missense variant replaces alanine with valine at codon 516 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 4/251422 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.

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