Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Supratech Reference Laboratories Pvt Ltd, |
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 |