ClinVar Miner

Submissions for variant NM_024426.6(WT1):c.1348C>T (p.His450Tyr)

dbSNP: rs28942089
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine RCV000003667 SCV002073217 likely pathogenic Drash syndrome criteria provided, single submitter clinical testing The missense variant p.H450Y in WT1 (NM_024426.6) chas been reported previously as His377Tyr in an affected patient with Denys Drasch syndrome (Jeanpierre, C et al). The variant has been submitted to ClinVar as Pathogenic but no functional studies have been reported. The p.H450Y variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The p.H450Y missense variant is predicted to be damaging by both SIFT and PolyPhen2. The histidine residue at codon 450 of WT1 is conserved in all mammalian species. The nucleotide c.1348 in WT1 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic.
Invitae RCV002512715 SCV003439688 pathogenic Drash syndrome; Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome 2022-10-09 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 445 of the WT1 protein (p.His445Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of Denys-Drash syndrome (PMID: 1327525, 9529364). In at least one individual the variant was observed to be de novo. This variant is also known as His377Tyr. ClinVar contains an entry for this variant (Variation ID: 3495). 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. This variant disrupts the p.His445 amino acid residue in WT1. Other variant(s) that disrupt this residue have been observed in individuals with WT1-related conditions (PMID: 20562648, 21851196), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000003667 SCV000023830 pathogenic Drash syndrome 1998-04-01 no assertion criteria provided literature only
OMIM RCV000003668 SCV000023831 pathogenic Nephrotic syndrome, type 4 1998-04-01 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.