ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.250G>A (p.Val84Met) (rs5030827)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492467 SCV000580992 likely pathogenic Hereditary cancer-predisposing syndrome 2017-10-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000767245 SCV000897789 uncertain significance Von Hippel-Lindau syndrome 2018-08-01 criteria provided, single submitter clinical testing
Invitae RCV000631269 SCV000752297 uncertain significance Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2017-12-24 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 84 of the VHL protein (p.Val84Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with von Hippel-Lindau (VHL) syndrome in a family (PMID: 17688370). This variant is also known as c.463G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 428813). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). A different missense substitution at this codon (p.Val84Leu) has been determined to be pathogenic (PMID: 8592333, 16502427, 25078357, 11331612). This suggests that the valine residue is critical for VHL protein function and that other missense substitutions at this position may also be pathogenic. 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.