Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001372063 | SCV001568651 | uncertain significance | Asphyxiating thoracic dystrophy 5; Senior-Loken syndrome 8 | 2020-08-20 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs774806370, ExAC 0.001%). This sequence change replaces histidine with proline at codon 1155 of the WDR19 protein (p.His1155Pro). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and proline. This variant has not been reported in the literature in individuals with WDR19-related conditions. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. |
Broad Center for Mendelian Genomics, |
RCV001724304 | SCV001950431 | uncertain significance | Retinitis pigmentosa | 2021-04-01 | criteria provided, single submitter | curation | The p.His1155Pro variant in WDR19 was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PM2, PP3. Based on this evidence we have classified this variant as a Variant of Uncertain Significance. If you have any questions about the classification please reach out to the Pierce Lab. |