Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000525079 | SCV000657609 | uncertain significance | Drash syndrome; Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome | 2017-06-28 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with tyrosine at codon 465 of the WT1 protein (p.His465Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with steroid-resistant nephrotic syndrome (PMID: 25349199) and in individuals affected with acute myeloid leukemia (PMID: 25092143, 20016532). This variant has also been reported as c.1589C>T. 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, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and reported in affected individuals, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |