• delete

NM_000551.3(VHL):c.535G>A (p.Asp179Asn) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Apr 20, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000478979.1

Allele description

NM_000551.3(VHL):c.535G>A (p.Asp179Asn)

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_000551.3(VHL):c.535G>A (p.Asp179Asn)
HGVS:
  • NC_000003.12:g.10149858G>A
  • NG_008212.3:g.13224G>A
  • NG_046756.1:g.7620G>A
  • NM_000551.3:c.535G>A
  • NM_001354723.2:c.*89G>A
  • NM_198156.3:c.412G>A
  • NP_000542.1:p.Asp179Asn
  • NP_937799.1:p.Asp138Asn
  • LRG_322t1:c.535G>A
  • LRG_322:g.13224G>A
  • LRG_322p1:p.Asp179Asn
  • NC_000003.11:g.10191542G>A
Protein change:
D138N
Links:
dbSNP: rs767780451
NCBI 1000 Genomes Browser:
rs767780451
Molecular consequence:
  • NM_001354723.2:c.*89G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000551.3:c.535G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198156.3:c.412G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000568003GeneDxcriteria provided, single submitter
Uncertain significance
(Apr 20, 2017)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000568003.2

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

Description

This variant is denoted VHL c.535G>A at the cDNA level, p.Asp179Asn (D179N) at the protein level, and results in the change of an Aspartic Acid to an Asparagine (GAC>AAC). This variant was observed in a patient with isolated hemangioblastoma, whose unaffected, 63 year old parent also carried this variant (Woodward 2007). VHL Asp179Asn was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Aspartic Acid and Asparagine differ in some properties, this is considered a semi-conservative amino acid substitution. VHL Asp179Asn occurs at a position where amino acids with properties similar to Aspartic Acid are tolerated across species and is located in the Elongin C binding domain (Yuen 2009). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether VHL Asp179Asn is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.

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

Last Updated: May 10, 2021

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