Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000822133 | SCV000962922 | pathogenic | Drash syndrome; Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome | 2022-06-14 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 664113). This missense change has been observed in individual(s) with clinical features of WT1-related conditions (PMID: 32493750; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 495 of the WT1 protein (p.Arg495Gln). |
| Victorian Clinical Genetics Services, |
RCV004594121 | SCV005086584 | pathogenic | Nephrotic syndrome, type 4 | 2023-07-17 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0103 - Dominant negative is a known mechanism of disease in this gene and is associated with Denys-Drash syndrome (MIM#194080); Frasier syndrome (MIM#136680); Meacham syndrome (MIM#608978) and Nephrotic syndrome, type 4 (MIM#256370) (GeneReviews). Loss of function is a known mechanism of disease in this gene and is associated with Wilms tumour, type 1 (MIM#194070). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to glutamine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0502 - Missense variant with conflicting in silico predictions and high conservation. (I) 0601 - Variant is located in the Zinc finger 4 domain (NCBI, PMID: 32493750). (SP) 0703 - Another variant comparable to the one identified in this case has strong previous evidence for pathogenicity. p.(Arg495Gly) has been reported de novo in two individuals, one with differences of sex development (PMID: 32493750), and one with isolated congenital diaphragmatic hernia (PMID: 32719394). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. It has been reported de novo in at least three probands with differences of sex development (PMID: 32493750); and an individual with focal segmental glomerulosclerosis (FSGS) (this diagnostic laboratory classified the variant as a VUS in ClinVar. (SP) 1007 - No published functional evidence has been identified for this variant. (I) 1204 - This variant has been shown to be de novo in the proband (parental status not tested but assumed) (by segregation analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Seattle Children's Hospital Molecular Genetics Laboratory, |
RCV003446461 | SCV004174075 | pathogenic | Drash syndrome | no assertion criteria provided | clinical testing |