ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.74C>T (p.Pro25Leu)

gnomAD frequency: 0.00261  dbSNP: rs35460768
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 24
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000079211 SCV000111081 benign not specified 2012-12-18 criteria provided, single submitter clinical testing
Invitae RCV001082579 SCV000153955 benign Chuvash polycythemia; Von Hippel-Lindau syndrome 2024-02-01 criteria provided, single submitter clinical testing
GeneDx RCV000079211 SCV000169801 benign not specified 2013-12-11 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000126300 SCV000212721 benign Hereditary cancer-predisposing syndrome 2015-07-09 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia RCV000119213 SCV000257721 benign Von Hippel-Lindau syndrome 2015-07-09 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000224298 SCV000281295 likely benign not provided 2015-10-05 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
PreventionGenetics, part of Exact Sciences RCV000079211 SCV000305277 benign not specified 2018-02-23 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000119213 SCV000439634 benign Von Hippel-Lindau syndrome 2018-03-06 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Genetic Services Laboratory, University of Chicago RCV000079211 SCV000597845 benign not specified 2017-04-27 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000224298 SCV000605561 benign not provided 2023-10-13 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000224298 SCV000780755 likely benign not provided 2024-03-01 criteria provided, single submitter clinical testing VHL: BS2
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV000224298 SCV002011306 likely benign not provided 2021-11-03 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000126300 SCV002534201 benign Hereditary cancer-predisposing syndrome 2020-07-21 criteria provided, single submitter curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000079211 SCV002552393 likely benign not specified 2023-08-15 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000119213 SCV004360950 benign Von Hippel-Lindau syndrome 2018-03-23 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000079211 SCV004847571 benign not specified 2023-07-07 criteria provided, single submitter clinical testing The p.Pro25Leu variant in VHL is classified as likely benign because it has been identified in 0.66% (23/3470) of Ashkenazi Jewish chromosomes and 0.45% (304/68032) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant was shown not to segregate with disease in 2 affected individuals from 2 families. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. ACMG/AMP Criteria applied: BS1, BS4, BP4.
ITMI RCV000079211 SCV000086484 not provided not specified 2013-09-19 no assertion provided reference population
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000224298 SCV001739990 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000224298 SCV001807641 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000079211 SCV001929331 benign not specified no assertion criteria provided clinical testing
Clinical Genomics Labs, University Health Network RCV000119213 SCV001950146 likely benign Von Hippel-Lindau syndrome 2019-07-12 no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000079211 SCV001957553 benign not specified no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000079211 SCV001966110 benign not specified no assertion criteria provided clinical testing
Baylor-Hopkins Center for Mendelian Genomics, Johns Hopkins University School of Medicine RCV002467563 SCV002764261 likely pathogenic Maffucci syndrome flagged submission research

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.