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NM_000551.4(VHL):c.109G>T (p.Glu37Ter) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 12, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002554860.4

Allele description [Variation Report for NM_000551.4(VHL):c.109G>T (p.Glu37Ter)]

NM_000551.4(VHL):c.109G>T (p.Glu37Ter)

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.109G>T (p.Glu37Ter)
HGVS:
  • NC_000003.12:g.10141956G>T
  • NG_008212.3:g.5322G>T
  • NM_000551.4:c.109G>TMANE SELECT
  • NM_001354723.2:c.109G>T
  • NM_198156.3:c.109G>T
  • NP_000542.1:p.Glu37Ter
  • NP_001341652.1:p.Glu37Ter
  • NP_937799.1:p.Glu37Ter
  • LRG_322:g.5322G>T
  • NC_000003.11:g.10183640G>T
  • NC_000003.11:g.10183640G>T
Protein change:
E37*
Links:
dbSNP: rs1338996432
NCBI 1000 Genomes Browser:
rs1338996432
Molecular consequence:
  • NM_000551.4:c.109G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354723.2:c.109G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_198156.3:c.109G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Chuvash polycythemia
Synonyms:
POLYCYTHEMIA, VHL-DEPENDENT; Erythrocytosis, familial, 2
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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002997379Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(May 12, 2022) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A second major native von Hippel-Lindau gene product, initiated from an internal translation start site, functions as a tumor suppressor.

Schoenfeld A, Davidowitz EJ, Burk RD.

Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8817-22.

PubMed [citation]
PMID:
9671762
PMCID:
PMC21160

pVHL19 is a biologically active product of the von Hippel-Lindau gene arising from internal translation initiation.

Iliopoulos O, Ohh M, Kaelin WG Jr.

Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11661-6.

PubMed [citation]
PMID:
9751722
PMCID:
PMC21697
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002997379.2

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

Description

This sequence change creates a premature translational stop signal (p.Glu37*) in the VHL gene. It is unclear whether it will result in an absent or disrupted protein product because an in-frame methionine located at codon 54 has the potential to rescue this variant. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with VHL-related conditions. ClinVar contains an entry for this variant (Variation ID: 872483). Several studies have shown that the VHL protein created from a downstream methionine located at codon 54 is biologically active, and exhibits properties similar to the full-length, wild-type protein (PMID: 9671762, 9751722). 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 8, 2024