ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.462A>G (p.Pro154=) (rs1060503562)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000474447 SCV000553406 uncertain significance Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2018-11-09 criteria provided, single submitter clinical testing This sequence change affects codon 154 of the VHL mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the VHL protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with VHL-related disease.  ClinVar contains an entry for this variant (Variation ID: 411977). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. A different variant (c.462A>C) affecting this nucleotide with the same silent change has been reported to segregate with disease in families affected with von Hippel-Lindau syndrome (PMID: 9829912, 17006605), and experimental studies suggest that this nucleotide may be crucial for normal mRNA splicing (PMID: 17006605). 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.