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NM_000551.4(VHL):c.407T>G (p.Phe136Cys)

Conflicting interpretations of pathogenicity​

Pathogenic(1);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
2 (Most recent: Jan 10, 2019)
Last evaluated:
Aug 1, 2018
Variation ID:
single nucleotide variant

NM_000551.4(VHL):c.407T>G (p.Phe136Cys)

Allele ID
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
Genomic location
3: 10146580 (GRCh38) GRCh38 UCSC
3: 10188264 (GRCh37) GRCh37 UCSC
Nucleotide Protein Molecular
... more HGVS
Protein change
Other names
Canonical SPDI
Functional consequence
Global minor allele frequency (GMAF)

Allele frequency
ClinGen: CA70049495
dbSNP: rs5030833

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 1 criteria provided, single submitter Feb 10, 2016 RCV000589290.1
Uncertain significance 1 criteria provided, single submitter Aug 1, 2018 RCV000767268.1
Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
VHL Sufficient evidence for dosage pathogenicity No evidence available GRCh38
550 1356
LOC107303340 - - - GRCh38 - 775

Submitted interpretations and evidence

(Last evaluated)
Review status
(Assertion criteria)
Submitter Supporting information
(Feb 10, 2016)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000697514.1
Submitted: (Jan 25, 2018)
Evidence details
PubMed (9)
Variant summary: VHL c.407T>G variant affects a conserved nucleotide, resulting in amino acid change from an aromatic Phe to a medium sized polar Cys. 4/4 … (more)
Uncertain significance
(Aug 01, 2018)
criteria provided, single submitter
Method: clinical testing
von Hippel-Lindau syndrome
Allele origin: germline
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia
Accession: SCV000897819.1
Submitted: (Jan 10, 2019)
Evidence details

Functional evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

Title Author Journal Year Link
Functional and oncologic outcomes of partial adrenalectomy for pheochromocytoma in patients with von Hippel-Lindau syndrome after at least 5 years of followup. Benhammou JN The Journal of urology 2010 PMID: 20846682
Computational detection of deleterious SNPs and their effect on sequence and structural level of the VHL gene. Rajasekaran R Mammalian genome : official journal of the International Mammalian Genome Society 2008 PMID: 18836774
Tat-binding protein-1, a component of the 26S proteasome, contributes to the E3 ubiquitin ligase function of the von Hippel-Lindau protein. Corn PG Nature genetics 2003 PMID: 14556007
Germ-line mutations in nonsyndromic pheochromocytoma. Neumann HP The New England journal of medicine 2002 PMID: 12000816
DHPLC-based germline mutation screening in the analysis of the VHL tumor suppressor gene: usefulness and limitations. Klein B Human genetics 2001 PMID: 11409863
VHL alterations in human clear cell renal cell carcinoma: association with advanced tumor stage and a novel hot spot mutation. Brauch H Cancer research 2000 PMID: 10766184
The impact of molecular genetic analysis of the VHL gene in patients with haemangioblastomas of the central nervous system. Gläsker S Journal of neurology, neurosurgery, and psychiatry 1999 PMID: 10567493
Germline mutations in the Von Hippel-Lindau disease (VHL) gene in families from North America, Europe, and Japan. Zbar B Human mutation 1996 PMID: 8956040
Germ-line mutations in the von Hippel-Lindau tumor-suppressor gene are similar to somatic von Hippel-Lindau aberrations in sporadic renal cell carcinoma. Whaley JM American journal of human genetics 1994 PMID: 7977367

Text-mined citations for rs5030833...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 24, 2021