ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.250G>C (p.Val84Leu) (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 RCV000216720 SCV000273215 pathogenic Hereditary cancer-predisposing syndrome 2015-01-02 criteria provided, single submitter clinical testing Rarity in general population databases (dbsnp, esp, 1000 genomes);Well-characterized mutation at same position;Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Integrated Genetics/Laboratory Corporation of America RCV000588802 SCV000697488 pathogenic Von Hippel-Lindau syndrome 2016-01-29 criteria provided, single submitter clinical testing Variant summary: This c.250G>C variant affects a conserved nucleotide, resulting in amino acid change from Val to Leu in beta domain of VHL protein. 2/4 in-silico tools predict this variant to be damaging. This variant was not found in approximately 99326 chromosomes from ExAC. This variant has been reported in one VHL patient as a de novo occurrence (Leonardi_2011) and in other two VHL patients as somatic occurrence (Burnichon_2011, Pena-Llopis_2013). Another nucleotide change c.250G>T leading to the same amino acid change is a known pathogenic variant, strongly supporting that this nucleotide change is also pathogenic. Functional studies show that p.V84L mutant impairs in forming stable pVHL-ElonginC-ElonginB (VCB) complexes which is implicated in the disease (Knauth_2009). Taken together, this variant has been classified as a Pathogenic.
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000588802 SCV000897790 pathogenic Von Hippel-Lindau syndrome 2018-08-01 criteria provided, single submitter 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.