ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.224_226TCT[1] (p.Phe76del) (rs5030648)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000469401 SCV000553395 pathogenic Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2019-03-13 criteria provided, single submitter clinical testing This sequence change deletes 3 nucleotides from exon 1 of the VHL mRNA (c.227_229delTCT). This leads to the deletion of 1 amino acid residue in the VHL protein (p.Phe76del) but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with von Hippel-Lindau syndrome in multiple families (PMID: 20064270, 27439424). It has also been reported in many other sporadic and familial cases (PMID: 12114495, 17661816, 18446368, 20151405, 20567917, 22357542, 27527340), including in an individual in whom the variant arose de novo (PMID: 23632291). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics,PreventionGenetics RCV000679023 SCV000805328 pathogenic not provided 2016-03-10 criteria provided, single submitter clinical testing
CIViC knowledgebase,Washington University School of Medicine RCV000208790 SCV001192830 pathogenic Von Hippel-Lindau syndrome criteria provided, single submitter curation The inframe variant, F76del, is pathogenic for Von Hippel-Lindau Disease. EID5682 shows a large family with the variant cosegregating with affected individuals (PP1). However, confirmed de novo mutations are also described EID5340 (PS2). Both are supported by several other reports with familial and sporadic VHL and this variant. This inframe deletion is not in a repetitive region (PM4) and absent from gnomAD v2.1 (PM2).
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000208790 SCV001365606 pathogenic Von Hippel-Lindau syndrome 2019-12-03 criteria provided, single submitter clinical testing The p.Phe76del variant in VHL has been reported in >15 individuals with clinical features of Von Hippel-Lindau syndrome and segregated with disease in >5 affected individuals from several families (Crossey 1994, Cybulski 2002, Gomy 2010, Hes 2007, Jia 2013, Lee 2016, Nordstrom-Obrien 2010, Pandit 2016, Rasmussen 2010, Wang 2018, Wong 2016, Wu 2012, Zhang 2008). It was also identified as a de novo occurrence in 1 individual, though maternity and paternity were not confirmed (Jia 2013). This variant has also been reported by other clinical laboratories in ClinVar (Variation ID 223166) and was absent from large population studies. This variant is a deletion of 1 amino acid at position 76 and is not predicted to alter the protein reading-frame. In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant Von Hippel- Lindau syndrome. ACMG/AMP criteria applied: PS4, PM2, PM6, PP1_Moderate, PM4_Supporting.
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000208790 SCV000264675 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.