ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.1A>G (p.Met1Val) (rs1060503557)

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 RCV000662755 SCV000785543 uncertain significance Von Hippel-Lindau syndrome 2017-09-06 criteria provided, single submitter clinical testing
Invitae RCV001230391 SCV001402868 uncertain significance Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2019-10-23 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the VHL mRNA. The next in-frame methionine is located at codon 54. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals with VHL-related conditions. ClinVar contains an entry for this variant (Variation ID: 548790). 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). Based on these results, the impact of this variant on VHL protein function is uncertain. 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.

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.