Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Medicine Center, |
RCV001280531 | SCV001366133 | pathogenic | Drash syndrome; Frasier syndrome | 2020-07-01 | criteria provided, single submitter | clinical testing | female infant with acute kidney, heart & respiratory failure |
Invitae | RCV001879755 | SCV002191457 | pathogenic | Drash syndrome; Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome | 2022-11-29 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 973193). This variant is also known as 373H to Q. This missense change has been observed in individual(s) with clinical features of autosomal dominant Denys-Drash syndrome (PMID: 8388765). 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 histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 441 of the WT1 protein (p.His441Gln). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt WT1 protein function. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.His441 amino acid residue in WT1. Other variant(s) that disrupt this residue have been observed in individuals with WT1-related conditions (PMID: 8956030), which suggests that this may be a clinically significant amino acid residue. |