ClinVar Miner

Submissions for variant NM_024426.6(WT1):c.404C>T (p.Pro135Leu)

gnomAD frequency: 0.00001  dbSNP: rs769642496
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000458098 SCV000545488 uncertain significance Drash syndrome; Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome 2023-12-07 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 130 of the WT1 protein (p.Pro130Leu). This variant is present in population databases (rs769642496, gnomAD 0.002%). This missense change has been observed in individual(s) with azoospermia (PMID: 25451826). ClinVar contains an entry for this variant (Variation ID: 406681). 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.
Mendelics RCV000988520 SCV001138268 uncertain significance Drash syndrome 2019-05-28 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004000749 SCV004826528 uncertain significance Wilms tumor 1 2023-08-15 criteria provided, single submitter clinical testing This missense variant replaces proline with leucine at codon 130 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 been reported in an individual affected with non-obstructive azoospermia patient (PMID: 25461826). This variant has been identified in 1/157016 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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