ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.91G>T (p.Glu31Ter) (rs1214275235)

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
Counsyl RCV000576425 SCV000677842 uncertain significance Von Hippel-Lindau syndrome 2017-05-10 criteria provided, single submitter clinical testing
Invitae RCV000532705 SCV000626922 uncertain significance Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2018-11-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 31 (p.Glu31*) of the VHL gene. It is unclear whether it will result in an absent or disrupted protein product because a highly conserved, in-frame methionine located at codon 54 has the potential to rescue the effect of this truncating variant. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a VHL-related disease. Downstream of the known ATG start site, the nearest methionine codon that can be used to initiate translation of the VHL protein lies at codon 54. Several studies have shown that the VHL protein created from this downstream methionine is biologically active, and exhibits properties similar to the full-length, wild-type protein (PMID: 9671762, 9751722, 10102622). Based on these results, the impact of this variant on VHL protein function is uncertain. In summary, this is a novel nonsense variant with uncertain impact on protein function. In the absence of additional data, it has been classified as a Variant of Uncertain Significance.

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.