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NM_000551.4(VHL):c.430G>A (p.Gly144Arg) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 26, 2024
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:
RCV002332473.3

Allele description [Variation Report for NM_000551.4(VHL):c.430G>A (p.Gly144Arg)]

NM_000551.4(VHL):c.430G>A (p.Gly144Arg)

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.430G>A (p.Gly144Arg)
HGVS:
  • NC_000003.12:g.10146603G>A
  • NG_008212.3:g.9969G>A
  • NG_046756.1:g.4365G>A
  • NM_000551.4:c.430G>AMANE SELECT
  • NM_001354723.2:c.*18-3184G>A
  • NM_198156.3:c.341-3184G>A
  • NP_000542.1:p.Gly144Arg
  • NP_000542.1:p.Gly144Arg
  • LRG_322t1:c.430G>A
  • LRG_322:g.9969G>A
  • LRG_322p1:p.Gly144Arg
  • NC_000003.11:g.10188287G>A
  • NM_000551.3:c.430G>A
Protein change:
G144R
Links:
dbSNP: rs869025650
NCBI 1000 Genomes Browser:
rs869025650
Molecular consequence:
  • NM_001354723.2:c.*18-3184G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_198156.3:c.341-3184G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000551.4:c.430G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002627580Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Mar 26, 2024) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Low frequency of VHL gene mutations in young individuals with polycythemia and high serum erythropoietin.

Randi ML, Murgia A, Putti MC, Martella M, Casarin A, Opocher G, Fabris F.

Haematologica. 2005 May;90(5):689-91.

PubMed [citation]
PMID:
15921386

An elusive phaeochromocytoma.

Yates CJ, McAuley SA, Grodski S, Hamblin PS, Ebeling PR.

Med J Aust. 2011 Jan 3;194(1):44-5. No abstract available.

PubMed [citation]
PMID:
21449869
See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV002627580.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

The p.G144R variant (also known as c.430G>A), located in coding exon 2 of the VHL gene, results from a G to A substitution at nucleotide position 430. The glycine at codon 144 is replaced by arginine, an amino acid with dissimilar properties. This alteration has been reported in an individual with a pheochromocytoma and in an individual with a paraganglioma (Yates CJ et al. Med J Aust, 2011 Jan;194:44-5; Favier J et al. Mod Pathol, 2020 01;33:57-64). It has also been reported in individuals affected with polycythemia and erythrocytosis, in the heterozygous state (Randi ML et al. Haematologica, 2005 May;90:689-91), and in conjunction with a second alteration in VHL (Bento C et al. Hum Mutat, 2014 Jan;35:15-26; Lenglet M et al. Blood, 2018 08;132:469-483). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 3, 2024