ClinVar Miner

Submissions for variant NM_024426.6(WT1):c.658C>A (p.Gln220Lys)

gnomAD frequency: 0.00001  dbSNP: rs373935628
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000810339 SCV000950534 uncertain significance Drash syndrome; Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome 2023-11-09 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 215 of the WT1 protein (p.Gln215Lys). This variant is present in population databases (rs373935628, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with WT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 654381). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on WT1 protein function. 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 RCV001776023 SCV002014027 uncertain significance not provided 2024-02-12 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
Fulgent Genetics, Fulgent Genetics RCV002487756 SCV002785579 uncertain significance Aniridia 1; Drash syndrome; Frasier syndrome; Meacham syndrome; Mesothelioma, malignant; Nephrotic syndrome, type 4; Wilms tumor 1; 11p partial monosomy syndrome 2021-07-08 criteria provided, single submitter clinical testing
Baylor Genetics RCV003461193 SCV004208930 uncertain significance Drash syndrome 2023-09-13 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004001722 SCV004829739 uncertain significance Wilms tumor 1 2023-08-08 criteria provided, single submitter clinical testing This missense variant replaces glutamine with lysine at codon 215 of the WT1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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 2/244208 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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