U.S. flag

An official website of the United States government

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

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 18, 2024
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:
RCV001382230.6

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:
Chuvash polycythemia
Synonyms:
POLYCYTHEMIA, VHL-DEPENDENT; Erythrocytosis, familial, 2
Identifiers:
MONDO: MONDO:0009892; MedGen: C1837915; Orphanet: 238557; OMIM: 263400
Name:
Von Hippel-Lindau syndrome (VHLS)
Synonyms:
VHL syndrome; Von Hippel-Lindau
Identifiers:
MONDO: MONDO:0008667; MedGen: C0019562; Orphanet: 892; OMIM: 193300

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
SCV001580902Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Jan 18, 2024)
germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Germline mutations in the von Hippel-Lindau disease tumor suppressor gene: correlations with phenotype.

Chen F, Kishida T, Yao M, Hustad T, Glavac D, Dean M, Gnarra JR, Orcutt ML, Duh FM, Glenn G, et al.

Hum Mutat. 1995;5(1):66-75.

PubMed [citation]
PMID:
7728151

Germline mutations in the von Hippel-Lindau disease (VHL) gene in Japanese VHL. Clinical Research Group for VHL in Japan.

[No authors listed]

Hum Mol Genet. 1995 Dec;4(12):2233-7.

PubMed [citation]
PMID:
8634692
See all PubMed Citations (7)

Details of each submission

From Invitae, SCV001580902.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 86 of the VHL protein (p.Pro86Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with von Hippel-Lindau (VHL) syndrome (PMID: 7728151, 27527340; Invitae). It has also been observed to segregate with disease in related individuals. This variant is also known as c.470C>T, p.Pro157Leu. ClinVar contains an entry for this variant (Variation ID: 182977). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt VHL protein function with a positive predictive value of 95%. This variant disrupts the p.Pro86 amino acid residue in VHL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8634692, 9829912, 19464396, 27057652, 27527340). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: May 1, 2024