ClinVar Miner

Submissions for variant NM_024426.6(WT1):c.671C>T (p.Thr224Met)

dbSNP: rs779451877
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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 RCV000803467 SCV000943339 uncertain significance Drash syndrome; Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome 2023-12-16 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 219 of the WT1 protein (p.Thr219Met). This variant is present in population databases (rs779451877, gnomAD 0.0009%). 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: 648686). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
All of Us Research Program, National Institutes of Health RCV004001664 SCV004828899 uncertain significance Wilms tumor 1 2024-02-05 criteria provided, single submitter clinical testing This missense variant replaces threonine with methionine at codon 219 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 1/249996 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 RCV004777877 SCV005389748 uncertain significance not provided 2024-04-01 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 8486616)
Ambry Genetics RCV005298617 SCV005967085 uncertain significance Inborn genetic diseases 2025-02-26 criteria provided, single submitter clinical testing The p.T219M variant (also known as c.656C>T), located in coding exon 2 of the WT1 gene, results from a C to T substitution at nucleotide position 656. The threonine at codon 219 is replaced by methionine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.

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