ClinVar Miner

Submissions for variant NM_024426.6(WT1):c.17T>C (p.Leu6Pro)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003789992 SCV004577104 uncertain significance Drash syndrome; Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome 2023-10-24 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the WT1 mRNA. The next in-frame methionine is located at codon 69. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with WT1-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Downstream of the non-canonical translation start site (CTG) at codon 1, the nearest methionine codon that can be used to initiate translation of the WT1 protein lies at codon 69. This downstream in-frame ATG is known as a major initiation site (PMID: 28811308, 16987884, 8621495). The functional significance of the different WT1 protein isoforms is unknown (PMID: 8621495), however mice lacking the N-terminal 68 amino acids develop normally and are fertile (PMID: 12640141). Based on these results, the impact of this variant on WT1 protein function is uncertain. 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.

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