ClinVar Miner

Submissions for variant NM_024426.6(WT1):c.1559T>C (p.Leu520Pro)

gnomAD frequency: 0.00001  dbSNP: rs774228907
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001209411 SCV001380843 uncertain significance Drash syndrome; Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome 2023-07-29 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 515 of the WT1 protein (p.Leu515Pro). This variant is present in population databases (rs774228907, gnomAD 0.003%). 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: 939929). 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) performed at Invitae indicates that this missense variant is not expected to disrupt 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.
Fulgent Genetics, Fulgent Genetics RCV002484134 SCV002781656 uncertain significance Aniridia 1; Drash syndrome; Frasier syndrome; Meacham syndrome; Mesothelioma, malignant; Nephrotic syndrome, type 4; Wilms tumor 1; 11p partial monosomy syndrome 2021-10-29 criteria provided, single submitter clinical testing
Ambry Genetics RCV002561713 SCV003651842 uncertain significance Inborn genetic diseases 2022-09-27 criteria provided, single submitter clinical testing The c.1544T>C (p.L515P) alteration is located in exon 10 (coding exon 10) of the WT1 gene. This alteration results from a T to C substitution at nucleotide position 1544, causing the leucine (L) at amino acid position 515 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV004570452 SCV005055860 uncertain significance Drash syndrome 2024-03-08 criteria provided, single submitter clinical testing
GeneDx RCV004590225 SCV005079402 uncertain significance not provided 2023-12-12 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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