NM_000551.4(VHL):c.463G>C (p.Val155Leu) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Jul 3, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001323712.1

Allele description [Variation Report for NM_000551.4(VHL):c.463G>C (p.Val155Leu)]

NM_000551.4(VHL):c.463G>C (p.Val155Leu)

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.463G>C (p.Val155Leu)
HGVS:
  • NC_000003.12:g.10146636G>C
  • NG_008212.3:g.10002G>C
  • NG_046756.1:g.4398G>C
  • NM_000551.4:c.463G>CMANE SELECT
  • NM_001354723.2:c.*18-3151G>C
  • NM_198156.3:c.341-3151G>C
  • NP_000542.1:p.Val155Leu
  • LRG_322t1:c.463G>C
  • LRG_322:g.10002G>C
  • NC_000003.11:g.10188320G>C
  • NM_000551.3:c.463G>C
Protein change:
V155L
Molecular consequence:
  • NM_001354723.2:c.*18-3151G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_198156.3:c.341-3151G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000551.4:c.463G>C - 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
SCV001514639Invitaecriteria provided, single submitter
Uncertain significance
(Jul 3, 2020)
germlineclinical testing

PubMed (3)
[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

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]
PMID:
17576681
PMCID:
PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]
PMID:
9536098
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001514639.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces valine with leucine at codon 155 of the VHL protein (p.Val155Leu). The valine residue is highly conserved and there is a small physicochemical difference between valine and leucine. This variant also falls at the last nucleotide of exon 2 of the VHL coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with von Hippel-Lindau (VHL) syndrome (Invitae). 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 C2). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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: Sep 29, 2021

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