ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.293A>G (p.Tyr98Cys) (rs864321643)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001218807 SCV001390711 pathogenic Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2019-06-05 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 98 of the VHL protein (p.Tyr98Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with clinical features of Von Hippel-Lindau syndrome (PMID: 12081237, 25720320, 29871882, 10761708, 25952756, Invitae). This variant is also known as 506A>G in the literature. ClinVar contains an entry for this variant (Variation ID: 223176). 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. This variant disrupts the p.Tyr98 amino acid residue in VHL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7759077, 21204227, 19763184, 11331612, 25371412, 11331613, 23840444, 16261165, 12510195, 10878807). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000208825 SCV000264696 pathogenic Von Hippel-Lindau syndrome 2016-02-26 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.