ClinVar Miner

Submissions for variant NM_024426.6(WT1):c.439C>G (p.Gln147Glu)

gnomAD frequency: 0.00001  dbSNP: rs953087575
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000463292 SCV000545503 uncertain significance Drash syndrome; Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome 2023-09-10 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 142 of the WT1 protein (p.Gln142Glu). This variant is present in population databases (no rsID available, gnomAD 0.001%). This variant has not been reported in the literature in individuals affected with WT1-related conditions. This missense change has been observed to be homozygous or hemizygous in an individual who did not have the expected clinical features for that genetic result (Invitae). ClinVar contains an entry for this variant (Variation ID: 406695). 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.
Sema4, Sema4 RCV002256257 SCV002530545 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-16 criteria provided, single submitter curation
Fulgent Genetics, Fulgent Genetics RCV002489024 SCV002782070 uncertain significance Aniridia 1; Drash syndrome; Frasier syndrome; Meacham syndrome; Mesothelioma, malignant; Nephrotic syndrome, type 4; Wilms tumor 1; 11p partial monosomy syndrome 2021-11-05 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004000753 SCV004816686 uncertain significance Wilms tumor 1 2023-10-30 criteria provided, single submitter clinical testing This variant replaces glutamine with glutamic acid at codon 142 in 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 3/224814 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.
Baylor Genetics RCV004567977 SCV005055855 uncertain significance Drash syndrome 2024-03-21 criteria provided, single submitter clinical testing
Breakthrough Genomics, Breakthrough Genomics RCV004696207 SCV005191242 uncertain significance not provided criteria provided, single submitter not provided

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