NM_000118.3(ENG):c.1586G>A (p.Arg529His) AND Hereditary hemorrhagic telangiectasia

Clinical significance:Likely pathogenic (Last evaluated: Aug 5, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000791433.3

Allele description [Variation Report for NM_000118.3(ENG):c.1586G>A (p.Arg529His)]

NM_000118.3(ENG):c.1586G>A (p.Arg529His)

Genes:
ENG:endoglin [Gene - OMIM - HGNC]
LOC102723566:uncharacterized LOC102723566 [Gene]
Variant type:
single nucleotide variant
Cytogenetic location:
9q34.11
Genomic location:
Preferred name:
NM_000118.3(ENG):c.1586G>A (p.Arg529His)
Other names:
p.R529H:CGC>CAC
HGVS:
  • NC_000009.12:g.127818220C>T
  • NG_009551.1:g.41549G>A
  • NM_000118.3:c.1586G>A
  • NM_001114753.2:c.1586G>A
  • NM_001278138.1:c.1040G>A
  • NP_000109.1:p.Arg529His
  • NP_001108225.1:p.Arg529His
  • NP_001265067.1:p.Arg347His
  • LRG_589t1:c.1586G>A
  • LRG_589t2:c.1586G>A
  • LRG_589:g.41549G>A
  • LRG_589p1:p.Arg529His
  • LRG_589p2:p.Arg529His
  • NC_000009.11:g.130580499C>T
  • NM_000118.2:c.1586G>A
  • P17813:p.Arg529His
  • p.(Arg529His)
Protein change:
R347H
Links:
UniProtKB: P17813#VAR_070299; dbSNP: rs863223538
NCBI 1000 Genomes Browser:
rs863223538
Molecular consequence:
  • NM_000118.3:c.1586G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001114753.2:c.1586G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001278138.1:c.1040G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary hemorrhagic telangiectasia (HHT)
Synonyms:
Osler Weber Rendu syndrome; ORW disease; Osler-Rendu-Weber disease; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0019180; MedGen: C0039445; OMIM: PS187300

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000283528Invitaecriteria provided, single submitter
Likely pathogenic
(Aug 5, 2020)
germlineclinical testing

PubMed (5)
[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

Clinical and analytical sensitivities in hereditary hemorrhagic telangiectasia testing and a report of de novo mutations.

Gedge F, McDonald J, Phansalkar A, Chou LS, Calderon F, Mao R, Lyon E, Bayrak-Toydemir P.

J Mol Diagn. 2007 Apr;9(2):258-65.

PubMed [citation]
PMID:
17384219
PMCID:
PMC1867450

Likelihood ratios to assess genetic evidence for clinical significance of uncertain variants: hereditary hemorrhagic telangiectasia as a model.

Bayrak-Toydemir P, McDonald J, Mao R, Phansalkar A, Gedge F, Robles J, Goldgar D, Lyon E.

Exp Mol Pathol. 2008 Aug;85(1):45-9. doi: 10.1016/j.yexmp.2008.03.006. Epub 2008 Apr 8.

PubMed [citation]
PMID:
18495117
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000283528.6

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

Description

This sequence change replaces arginine with histidine at codon 529 of the ENG protein (p.Arg529His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals and families affected with hereditary hemorrhagic telangiectasia (PMID: 17384219, 18495117, 16752392, 22991266, Invitae). ClinVar contains an entry for this variant (Variation ID: 213212). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: May 10, 2021

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