NM_000551.4(VHL):c.451A>G (p.Ile151Val) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Feb 16, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001063276.1

Allele description [Variation Report for NM_000551.4(VHL):c.451A>G (p.Ile151Val)]

NM_000551.4(VHL):c.451A>G (p.Ile151Val)

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.451A>G (p.Ile151Val)
HGVS:
  • NC_000003.12:g.10146624A>G
  • NG_008212.3:g.9990A>G
  • NG_046756.1:g.4386A>G
  • NM_000551.4:c.451A>GMANE SELECT
  • NM_001354723.2:c.*18-3163A>G
  • NM_198156.3:c.341-3163A>G
  • NP_000542.1:p.Ile151Val
  • LRG_322t1:c.451A>G
  • LRG_322:g.9990A>G
  • NC_000003.11:g.10188308A>G
  • NM_000551.3:c.451A>G
Protein change:
I151V
Molecular consequence:
  • NM_001354723.2:c.*18-3163A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_198156.3:c.341-3163A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000551.4:c.451A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Erythrocytosis, familial, 2 (ECYT2)
Synonyms:
POLYCYTHEMIA, CHUVASH TYPE; POLYCYTHEMIA, VHL-DEPENDENT
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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001228114Invitaecriteria provided, single submitter
Uncertain significance
(Feb 16, 2019)
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

The impact of molecular genetic analysis of the VHL gene in patients with haemangioblastomas of the central nervous system.

Gläsker S, Bender BU, Apel TW, Natt E, van Velthoven V, Scheremet R, Zentner J, Neumann HP.

J Neurol Neurosurg Psychiatry. 1999 Dec;67(6):758-62.

PubMed [citation]
PMID:
10567493
PMCID:
PMC1736691

Genotype-phenotype correlations in Chinese von Hippel-Lindau disease patients.

Peng S, Shepard MJ, Wang J, Li T, Ning X, Cai L, Zhuang Z, Gong K.

Oncotarget. 2017 Jun 13;8(24):38456-38465. doi: 10.18632/oncotarget.16594.

PubMed [citation]
PMID:
28388566
PMCID:
PMC5503545
See all PubMed Citations (7)

Details of each submission

From Invitae, SCV001228114.1

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

Description

This sequence change replaces isoleucine with valine at codon 151 of the VHL protein (p.Ile151Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with VHL-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). This variant disrupts the p.Ile151 amino acid residue in VHL. Other variants that disrupt this residue have been observed in individuals with VHL-related conditions (PMID: 10567493, 28469506, 22357542, 25078357, 28388566, 19814753), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: May 10, 2021

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