Submissions for variant NM_024426.6(WT1):c.791A>C (p.Gln264Pro)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002299790	SCV002589360	uncertain significance	Drash syndrome; Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome	2022-09-24	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with WT1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 259 of the WT1 protein (p.Gln259Pro). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65". The proline amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
PreventionGenetics, part of Exact Sciences	RCV004548268	SCV004105632	uncertain significance	WT1-related disorder	2023-08-05	criteria provided, single submitter	clinical testing	The WT1 c.776A>C variant is predicted to result in the amino acid substitution p.Gln259Pro. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.