Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001812376 | SCV001471642 | uncertain significance | not provided | 2020-08-24 | criteria provided, single submitter | clinical testing | The WDR19 p.Tyr1133His variant (rs1187864679), to our knowledge, has not been reported in the medical literature or gene specific databases. This variant is also absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The tyrosine at codon 1133 is highly conserved (Alamut v.2.11) and computational analyses (SIFT, PolyPhen-2) predict conflicting effects of this variant on protein structure/function. Based on the available information, the clinical significance of this variant is uncertain. |
| Invitae | RCV003770439 | SCV004578344 | uncertain significance | Asphyxiating thoracic dystrophy 5; Senior-Loken syndrome 8 | 2022-11-28 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 993600). This variant has not been reported in the literature in individuals affected with WDR19-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 1133 of the WDR19 protein (p.Tyr1133His). |