NM_000551.4(VHL):c.340+770T>C AND Erythrocytosis, familial, 2

Clinical significance:Pathogenic (Last evaluated: Jan 1, 2005)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_000551.4(VHL):c.340+770T>C]


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:
Genomic location:
Preferred name:
  • NC_000003.12:g.10142957T>C
  • NG_008212.3:g.6323T>C
  • NG_046756.1:g.719T>C
  • NM_000551.4:c.340+770T>CMANE SELECT
  • NM_001354723.2:c.535T>C
  • NM_198156.3:c.340+770T>C
  • NP_001341652.1:p.Ser179Pro
  • LRG_322t1:c.340+770T>C
  • LRG_322:g.6323T>C
  • NC_000003.11:g.10184641T>C
  • NM_000551.3:c.340+770T>C
  • c.340+770T-C
Protein change:
OMIM: 608537.0030; dbSNP: rs1346312258
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000551.4:c.340+770T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_198156.3:c.340+770T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354723.2:c.535T>C - missense variant - [Sequence Ontology: SO:0001583]


Erythrocytosis, familial, 2 (ECYT2)
MONDO: MONDO:0009892; MedGen: C1837915; Orphanet: 238557; OMIM: 263400

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)
SCV001167314OMIMno assertion criteria providedPathogenic
(Jan 1, 2005)
germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only



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]

Mutations in the von Hippel-Lindau (VHL) tumor suppressor gene and VHL-haplotype analysis in patients with presumable congenital erythrocytosis.

Cario H, Schwarz K, Jorch N, Kyank U, Petrides PE, Schneider DT, Uhle R, Debatin KM, Kohne E.

Haematologica. 2005 Jan;90(1):19-24.

PubMed [citation]

Details of each submission

From OMIM, SCV001167314.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)


In 4 patients from 3 unrelated families (F1, F2, and F3) with familial erythrocytosis-2 (ECYT2; 263400), Lenglet et al. (2018) identified compound heterozygous mutations in the VHL gene. All 4 patients carried a T-to-C transition (c.340+770T-C) in cryptic exon 1-prime (E1-prime), resulting in a splicing alteration, on 1 allele. Three patients from F2 and F3 had previously been diagnosed with Chuvash polycythemia since they were heterozygous for the R200W mutation (608537.0019) on the other allele. Prior to the study of Lenglet et al. (2018), these patients were thought to carry only 1 VHL mutation (the patient from F2 had previously been reported by Cario et al., 2005). The mutations, which were found by a combination of whole-genome and Sanger sequencing, segregated with the disorder in the families. RT-PCR analysis of lymphoblastoid cells from 1 patient (F1) showed a decrease in the exon 1/exon 2/exon 3 isoform and an increase in an exon 1/exon 3 isoform compared to wildtype. The patient from F1 carried a synonymous c.429C-T transition (asp143-to-asp, D143D) on the other allele, which also affected splicing. Two further unrelated patients with ECYT2 (families F9 and F10) were homozygous for the c.429C-T transition in the VHL gene. RT-PCR analysis from lymphocytes derived from these patients showed decreased mRNA levels, increased amounts of the E1/E3 transcripts, and severe decreases in the wildtype VHL mRNA and protein isoform compared to controls, suggesting that the mutation resulted in the skipping of exon 2. The 2 patients from families F9 and F10 also had mutations in the HBB gene (141900), which may have compensated for the ECYT2.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 10, 2021

Support Center