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NM_000551.4(VHL):c.378T>G (p.Asp126Glu) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 13, 2018
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:
RCV001021148.3

Allele description [Variation Report for NM_000551.4(VHL):c.378T>G (p.Asp126Glu)]

NM_000551.4(VHL):c.378T>G (p.Asp126Glu)

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.378T>G (p.Asp126Glu)
HGVS:
  • NC_000003.12:g.10146551T>G
  • NG_008212.3:g.9917T>G
  • NG_046756.1:g.4313T>G
  • NM_000551.4:c.378T>GMANE SELECT
  • NM_001354723.2:c.*18-3236T>G
  • NM_198156.3:c.341-3236T>G
  • NP_000542.1:p.Asp126Glu
  • LRG_322t1:c.378T>G
  • LRG_322:g.9917T>G
  • NC_000003.11:g.10188235T>G
  • NM_000551.3:c.378T>G
Protein change:
D126E
Links:
dbSNP: rs764053615
NCBI 1000 Genomes Browser:
rs764053615
Molecular consequence:
  • NM_001354723.2:c.*18-3236T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_198156.3:c.341-3236T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000551.4:c.378T>G - 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
SCV001182727Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Nov 13, 2018) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From Ambry Genetics, SCV001182727.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The p.D126E variant (also known as c.378T>G), located in coding exon 2 of the VHL gene, results from a T to G substitution at nucleotide position 378. The aspartic acid at codon 126 is replaced by glutamic acid, an amino acid with highly similar properties. A similar alteration affecting this same amino acid, p.D126N, has been shown to cause autosomal recessive polycythemia, a condition characterized by increased red blood cell mass and high risk of pulmonary hypertension, peripheral thrombosis and cerebrovascular events, but not Von Hippel-Lindau syndrome (Bond, J et al. Blood. 2011 Mar 31;117(13):3699-701). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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: May 1, 2024