NM_000551.4(VHL):c.500G>C (p.Arg167Pro) AND Hereditary cancer-predisposing syndrome

Clinical significance:Pathogenic (Last evaluated: Aug 28, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000492510.1

Allele description [Variation Report for NM_000551.4(VHL):c.500G>C (p.Arg167Pro)]

NM_000551.4(VHL):c.500G>C (p.Arg167Pro)

Genes:
LOC107303340:3p25 von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase Alu-mediated recombination region [Gene]
VHL:von Hippel-Lindau tumor suppressor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p25.3
Genomic location:
Preferred name:
NM_000551.4(VHL):c.500G>C (p.Arg167Pro)
HGVS:
  • NC_000003.12:g.10149823G>C
  • NG_008212.3:g.13189G>C
  • NG_046756.1:g.7585G>C
  • NM_000551.3:c.500G>C
  • NM_000551.4:c.500G>CMANE SELECT
  • NM_001354723.2:c.*54G>C
  • NM_198156.3:c.377G>C
  • NP_000542.1:p.Arg167Pro
  • NP_000542.1:p.Arg167Pro
  • NP_937799.1:p.Arg126Pro
  • LRG_322t1:c.500G>C
  • LRG_322:g.13189G>C
  • LRG_322p1:p.Arg167Pro
  • NC_000003.11:g.10191507G>C
Protein change:
R126P
Links:
dbSNP: rs5030821
NCBI 1000 Genomes Browser:
rs5030821
Molecular consequence:
  • NM_001354723.2:c.*54G>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000551.3:c.500G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000551.4:c.500G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198156.3:c.377G>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MedGen: C0027672

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000580969Ambry Geneticscriteria provided, single submitter
Pathogenic
(Aug 28, 2018)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Genotype-phenotype correlations in von Hippel-Lindau disease.

Ong KR, Woodward ER, Killick P, Lim C, Macdonald F, Maher ER.

Hum Mutat. 2007 Feb;28(2):143-9.

PubMed [citation]
PMID:
17024664

Pilot trial of sunitinib therapy in patients with von Hippel-Lindau disease.

Jonasch E, McCutcheon IE, Waguespack SG, Wen S, Davis DW, Smith LA, Tannir NM, Gombos DS, Fuller GN, Matin SF.

Ann Oncol. 2011 Dec;22(12):2661-2666. doi: 10.1093/annonc/mdr011.

PubMed [citation]
PMID:
22105611
PMCID:
PMC4542805
See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV000580969.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (5)

Description

The p.R167P pathogenic mutation (also known as c.500G>C), located in coding exon 3 of the VHL gene, results from a G to C substitution at nucleotide position 500. The arginine at codon 167 is replaced by proline, an amino acid with dissimilar properties. This mutation has been identified in multiple von Hippel-Lindau disease cohorts (Bausch B et al. Head Neck, 2016 Apr;38 Suppl 1:E673-9; Jonasch E et al. Ann. Oncol., 2011 Dec;22:2661-6; Peng S et al. Oncotarget, 2017 Jun;8:38456-38465). In addition, several other mutations affecting codon 167 have been chacterized in VHL patients (Ong KR et al. Hum. Mutat., 2007 Feb;28:143-9; Crossey PA et al. Hum. Mol. Genet., 1994 Aug;3:1303-8). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Oct 25, 2021

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