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NM_000551.4(VHL):c.257C>G (p.Pro86Arg) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 28, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002426981.10

Allele description [Variation Report for NM_000551.4(VHL):c.257C>G (p.Pro86Arg)]

NM_000551.4(VHL):c.257C>G (p.Pro86Arg)

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.257C>G (p.Pro86Arg)
HGVS:
  • NC_000003.12:g.10142104C>G
  • NG_008212.3:g.5470C>G
  • NM_000551.4:c.257C>GMANE SELECT
  • NM_001354723.2:c.257C>G
  • NM_198156.3:c.257C>G
  • NP_000542.1:p.Pro86Arg
  • NP_000542.1:p.Pro86Arg
  • NP_001341652.1:p.Pro86Arg
  • NP_937799.1:p.Pro86Arg
  • LRG_322t1:c.257C>G
  • LRG_322:g.5470C>G
  • LRG_322p1:p.Pro86Arg
  • NC_000003.11:g.10183788C>G
  • NM_000551.3:c.257C>G
  • P40337:p.Pro86Arg
  • p.[Pro86Arg]
Protein change:
P86R
Links:
UniProtKB: P40337#VAR_005695; dbSNP: rs730882034
NCBI 1000 Genomes Browser:
rs730882034
Molecular consequence:
  • NM_000551.4:c.257C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354723.2:c.257C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198156.3:c.257C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002740355Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jul 28, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Is the P25L a "real" VHL mutation?

Rothberg PG, Bradley JF, Baker DW, Huelsman KM.

Mol Diagn. 2001 Mar;6(1):49-54.

PubMed [citation]
PMID:
11257211

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
See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV002740355.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

The p.P86R pathogenic mutation (also known as c.257C>G), located in coding exon 1 of the VHL gene, results from a C to G substitution at nucleotide position 257. The proline at codon 86 is replaced by arginine, an amino acid with dissimilar properties. This variant has been reported in numerous families with a diagnosis of Von Hippel-Lindau syndrome (VHL) (Stolle C et al. Hum. Mutat. 1998;12:417-23; Rothberg PG et al. Mol. Diagn. 2001 Mar;6:49-54; Ong KR et al. Hum. Mutat. 2007 Feb;28:143-9; Liu SJ et al. Genet. Med. 2018 10;20:1266-1273). Of note, the p.P86L (c.257C>T) alteration has also been reported as p.P157L (c.470C>T) in some literature. Several other alterations at the same codon (p.P86A, p.P86L, and p.P86S) have been detected in individuals with VHL syndrome suggesting this codon may represent a mutation hotspot. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 8, 2024