NM_000551.4(VHL):c.610G>T (p.Glu204Ter) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Dec 19, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000631268.2

Allele description [Variation Report for NM_000551.4(VHL):c.610G>T (p.Glu204Ter)]

NM_000551.4(VHL):c.610G>T (p.Glu204Ter)

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.610G>T (p.Glu204Ter)
HGVS:
  • NC_000003.12:g.10149933G>T
  • NG_008212.3:g.13299G>T
  • NG_046756.1:g.7695G>T
  • NM_000551.3:c.610G>T
  • NM_000551.4:c.610G>TMANE SELECT
  • NM_001354723.2:c.*164G>T
  • NM_198156.3:c.487G>T
  • NP_000542.1:p.Glu204Ter
  • NP_000542.1:p.Glu204Ter
  • NP_937799.1:p.Glu163Ter
  • LRG_322t1:c.610G>T
  • LRG_322:g.13299G>T
  • LRG_322p1:p.Glu204Ter
  • NC_000003.11:g.10191617G>T
  • NC_000003.11:g.10191617G>T
Protein change:
E163*
Links:
dbSNP: rs758853661
NCBI 1000 Genomes Browser:
rs758853661
Molecular consequence:
  • NM_001354723.2:c.*164G>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000551.3:c.610G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_000551.4:c.610G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_198156.3:c.487G>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000752296Invitaecriteria provided, single submitter
Uncertain significance
(Dec 19, 2019)
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

Role of the C-terminal alpha-helical domain of the von Hippel-Lindau protein in its E3 ubiquitin ligase activity.

Lewis MD, Roberts BJ.

Oncogene. 2004 Mar 25;23(13):2315-23.

PubMed [citation]
PMID:
14691445

Molecular pathology of von HippelLindau disease and the VHL tumour suppressor gene.

Richards FM.

Expert Rev Mol Med. 2001 Mar 19;2001:1-27. doi: 10.1017/S1462399401002654. No abstract available.

PubMed [citation]
PMID:
14987375
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000752296.3

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

Description

This sequence change results in a premature translational stop signal in the VHL gene (p.Glu204*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 10 amino acids of the VHL protein. This variant is present in population databases (rs758853661, ExAC 0.009%). This variant has not been reported in the literature in individuals with VHL-related disease. This variant is expected to delete a portion of the C-terminal region of the VHL protein near the β domain (a-helix) (PMID: 14691445, 14987375). Experimental studies are not available for this variant, and the functional significance of the deleted amino acids is currently unknown. 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: Oct 25, 2021

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