U.S. flag

An official website of the United States government

NM_000551.4(VHL):c.257C>T (p.Pro86Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 7, 2021
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:
RCV000492524.4

Allele description [Variation Report for NM_000551.4(VHL):c.257C>T (p.Pro86Leu)]

NM_000551.4(VHL):c.257C>T (p.Pro86Leu)

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>T (p.Pro86Leu)
HGVS:
  • NC_000003.12:g.10142104C>T
  • NG_008212.3:g.5470C>T
  • NM_000551.4:c.257C>TMANE SELECT
  • NM_001354723.2:c.257C>T
  • NM_198156.3:c.257C>T
  • NP_000542.1:p.Pro86Leu
  • NP_000542.1:p.Pro86Leu
  • NP_001341652.1:p.Pro86Leu
  • NP_937799.1:p.Pro86Leu
  • LRG_322t1:c.257C>T
  • LRG_322:g.5470C>T
  • LRG_322p1:p.Pro86Leu
  • NC_000003.11:g.10183788C>T
  • NM_000551.3:c.257C>T
  • P40337:p.Pro86Leu
  • p.[Pro86Leu]
Protein change:
P86L
Links:
UniProtKB: P40337#VAR_005694; dbSNP: rs730882034
NCBI 1000 Genomes Browser:
rs730882034
Molecular consequence:
  • NM_000551.4:c.257C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354723.2:c.257C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198156.3:c.257C>T - 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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000580955Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)
Pathogenic
(Oct 7, 2021)
germlineclinical testing

PubMed (10)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

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

Citations

PubMed

Germ-line mutation analysis in patients with von Hippel-Lindau disease in Japan: an extended study of 77 families.

Yoshida M, Ashida S, Kondo K, Kobayashi K, Kanno H, Shinohara N, Shitara N, Kishida T, Kawakami S, Baba M, Yamamoto I, Hosaka M, Shuin T, Yao M.

Jpn J Cancer Res. 2000 Feb;91(2):204-12.

PubMed [citation]
PMID:
10761708
PMCID:
PMC5926327

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 (10)

Details of each submission

From Ambry Genetics, SCV000580955.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (10)

Description

The p.P86L pathogenic mutation (also known as c.257C>T), located in coding exon 1 of the VHL gene, results from a C to T substitution at nucleotide position 257. The proline at codon 86 is replaced by leucine, an amino acid with very few similar properties. This pathogenic mutation has been found in multiple individuals meeting clinical criteria for Von Hippel-Lindau syndrome with symptoms including retinal angiomas, CNS hemangioblastomas, renal cell carcinoma, and pancreatic cysts/tumors (Chen F et al. Hum. Mutat. 1995; 5(1):66-75; Kondo et al. Hum. Mol. Genet. 1995 Dec;4(12):2233-7; Yoshida M et al. Jpn. J. Cancer Res. 2000 Feb; 91(2):204-12; Ong KR et al. Hum. Mutat. 2007 Feb;28(2):143-9; Zhang J et al J. Cancer Res. Clin. Oncol. 2008 Nov;134(11):1211-8; Wong M et al. Chin J Cancer. 2016 Aug;35:79). Three unique alterations located at the same position, p.P86A, p.P86S, and p.P86R, have each been documented in the literature as having an association with Von Hippel-Lindau syndrome suggesting this codon may represent a mutation hotspot. Of note, the p.P86L (c.257C>T) alteration has also been reported as p.P157L (c.470C>T) in some literature. 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: May 1, 2024