NM_000551.4(VHL):c.340+805C>G AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Sep 13, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001363927.1

Allele description [Variation Report for NM_000551.4(VHL):c.340+805C>G]

NM_000551.4(VHL):c.340+805C>G

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+805C>G
HGVS:
  • NC_000003.12:g.10142992C>G
  • NG_008212.3:g.6358C>G
  • NG_046756.1:g.754C>G
  • NM_000551.4:c.340+805C>GMANE SELECT
  • NM_001354723.2:c.570C>G
  • NM_198156.3:c.340+805C>G
  • NP_001341652.1:p.Ser190Arg
  • LRG_322:g.6358C>G
  • NC_000003.11:g.10184676C>G
Protein change:
S190R
Molecular consequence:
  • NM_000551.4:c.340+805C>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_198156.3:c.340+805C>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354723.2:c.570C>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
SCV001560059Invitaecriteria provided, single submitter
Uncertain significance
(Sep 13, 2020)
germlineclinical testing

PubMed (4)
[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

Identification of a new VHL exon and complex splicing alterations in familial erythrocytosis or von Hippel-Lindau disease.

Lenglet M, Robriquet F, Schwarz K, Camps C, Couturier A, Hoogewijs D, Buffet A, Knight SJL, Gad S, Couvé S, Chesnel F, Pacault M, Lindenbaum P, Job S, Dumont S, Besnard T, Cornec M, Dreau H, Pentony M, Kvikstad E, Deveaux S, Burnichon N, et al.

Blood. 2018 Aug 2;132(5):469-483. doi: 10.1182/blood-2018-03-838235. Epub 2018 Jun 11.

PubMed [citation]
PMID:
29891534

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
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001560059.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change falls in intron 1 of the VHL gene. It is not expected to change the encoded amino acid sequence of the VHL protein. However, this sequence change falls within a cryptic exon in the VHL gene, known as exon E1’, which is naturally expressed at low levels in several human tissues (PMID: 29891534). 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. 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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