ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.208G>A (p.Glu70Lys) (rs5030802)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492137 SCV000580979 likely pathogenic Hereditary cancer-predisposing syndrome 2017-10-09 criteria provided, single submitter clinical testing Rarity in general population databases (dbsnp, esp, 1000 genomes);Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;Deficient protein function in appropriate functional assay(s)
Integrated Genetics/Laboratory Corporation of America RCV000036540 SCV000697485 pathogenic Von Hippel-Lindau syndrome 2016-02-03 criteria provided, single submitter clinical testing Variant summary: The c.208G>A variant affects a conserved nucleotide, resulting in amino acid change from Glu to Lys. 4/4 in-silico tools predict benign outcome for this variant (SNPs&GO not captured due to low reliability index); however, these in silico predictions have not been verified with functional studies. This variant is found in 1/67270 control chromosomes at a frequency of 0.0000149, which does not significantly exceed maximal expected frequency of a pathogenic allele (0.0000208). This variant has been found in at least 10 unrelated VHL patients and is reported as the most common pathogenic variant in Korean patients (Hwang_2014). In addition, one clinical laboratory classified this variant as pathogenic. Taken together, this variant was classified as pathogenic.
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000036540 SCV000782417 pathogenic Von Hippel-Lindau syndrome 2016-11-01 criteria provided, single submitter clinical testing
CIViC knowledgebase,Washington University School of Medicine RCV000036540 SCV001192829 likely pathogenic Von Hippel-Lindau syndrome criteria provided, single submitter curation VHL E70K (c.208G>A) is Likely Pathogenic. E70K missense variant occurs at a very low allele frequency in the general population (0.00001489 allele frequency in ExAC, 4.365e-6 allele frequency in gnomAD) and was previously identified in several unrelated individuals with VHL disease symptoms (see evidence statements). PM1 (6860); PM2 (per above); PP1 (5805); PP4 (5805;6742).
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000036540 SCV000060195 pathogenic Von Hippel-Lindau syndrome 2007-04-11 no assertion criteria provided clinical testing
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000036540 SCV000264671 pathogenic Von Hippel-Lindau syndrome 2016-02-26 no assertion criteria provided 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.