NM_000551.4(VHL):c.340+646A>T AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Jun 22, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001042467.2

Allele description [Variation Report for NM_000551.4(VHL):c.340+646A>T]

NM_000551.4(VHL):c.340+646A>T

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.340+646A>T
HGVS:
  • NC_000003.12:g.10142833A>T
  • NG_008212.3:g.6199A>T
  • NG_046756.1:g.595A>T
  • NM_000551.4:c.340+646A>TMANE SELECT
  • NM_001354723.2:c.411A>T
  • NM_198156.3:c.340+646A>T
  • NP_001341652.1:p.Arg137Ser
  • LRG_322t1:c.340+646A>T
  • LRG_322:g.6199A>T
  • NC_000003.11:g.10184517A>T
  • NM_000551.3:c.340+646A>T
Protein change:
R137S
Molecular consequence:
  • NM_000551.4:c.340+646A>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_198156.3:c.340+646A>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354723.2:c.411A>T - 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
SCV001206149Invitaecriteria provided, single submitter
Uncertain significance
(Jun 22, 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, SCV001206149.2

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

Description

This sequence change falls in intron 1 of the VHL gene. It does not directly change the encoded amino acid sequence of the VHL protein, but it affects a nucleotide within the consensus splice site of the intron. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals with VHL-related conditions. ClinVar contains an entry for this variant (Variation ID: 840470). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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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