ClinVar Miner

Submissions for variant NM_024426.6(WT1):c.677C>T (p.Thr226Ile)

dbSNP: rs556804456
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000814091 SCV000954488 uncertain significance Drash syndrome; Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome 2018-08-15 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 221 of the WT1 protein (p.Thr221Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with WT1-related disease. This variant is present in population databases (rs556804456, ExAC 0.006%).
All of Us Research Program, National Institutes of Health RCV004001758 SCV004832085 uncertain significance Wilms tumor 1 2023-06-08 criteria provided, single submitter clinical testing This missense variant replaces threonine with isoleucine at codon 221 of 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 1/250298 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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