Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000544002 | SCV000657619 | uncertain significance | Drash syndrome; Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome | 2024-01-12 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 68 of the WT1 protein (p.Gln68Leu). This variant is present in population databases (no rsID available, gnomAD 0.002%). 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: 476696). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The leucine 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. |
| Gene |
RCV001591301 | SCV001823653 | uncertain significance | not provided | 2023-03-24 | criteria provided, single submitter | clinical testing | 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; Not observed at significant frequency in large population cohorts (gnomAD) |
| Sema4, |
RCV002256394 | SCV002530533 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-09 | criteria provided, single submitter | curation | |
| Fulgent Genetics, |
RCV002491099 | SCV002787229 | uncertain significance | Aniridia 1; Drash syndrome; Frasier syndrome; Meacham syndrome; Mesothelioma, malignant; Nephrotic syndrome, type 4; Wilms tumor 1; 11p partial monosomy syndrome | 2022-03-10 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002527933 | SCV003527366 | uncertain significance | Inborn genetic diseases | 2021-07-21 | criteria provided, single submitter | clinical testing | The c.203A>T (p.Q68L) alteration is located in exon 1 (coding exon 1) of the WT1 gene. This alteration results from a A to T substitution at nucleotide position 203, causing the glutamine (Q) at amino acid position 68 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Revvity Omics, |
RCV001591301 | SCV003823797 | uncertain significance | not provided | 2022-09-06 | criteria provided, single submitter | clinical testing | |
| Breakthrough Genomics, |
RCV001591301 | SCV005191243 | uncertain significance | not provided | criteria provided, single submitter | not provided | ||
| Victorian Clinical Genetics Services, |
RCV004787897 | SCV005398542 | likely benign | Nephrotic syndrome, type 4 | 2021-05-06 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely benign. Following criteria are met: 0103 - Dominant negative and loss of function are known mechanisms of disease in this gene and are associated with WT1-related disease. Variants predicted to undergo nonsense-mediated decay, and truncating variants lacking the zinc-finger motifs, have been reported with a loss of function (LOF) and dominant negative (DN) mechanism, respectively. Missense variants are have been functionally proven to have a LOF effect, however, more investigation is required to exclude if DN is also occurring (Decipher, GeneReviews, PMID: 26090994, PMID: 25145932). (I) 0107 - This gene is associated with autosomal dominant disease. The diseases were previously regarded as different syndromes, but are now considered part of a phenotypic continuum (GeneReviews). (I) 0113 - This gene is known to be imprinted (NCBI). Loss of imprinting in wilms tumours has been reported (PMID: 18644976). (I) 0200 - Variant is predicted to result in a missense amino acid change from glutamine to leucine. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v3) <0.001 for a dominant condition (3 heterozygotes, 0 homozygotes), but has been misannotated as p.(Gln73Leu). (SP) 0503 - Missense variant consistently predicted to be tolerated by multiple in silico tools or not conserved in placental mammals with a minor amino acid change. (SB) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0808 - Previous reports of pathogenicity for this variant are conflicting. This variant has been reported as likely benign and as a VUS (LOVD, ClinVar). (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |