NM_001114753.3(ENG):c.806T>G (p.Met269Arg) AND Hereditary hemorrhagic telangiectasia

Clinical significance:Pathogenic (Last evaluated: Sep 17, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_001114753.3(ENG):c.806T>G (p.Met269Arg)]

NM_001114753.3(ENG):c.806T>G (p.Met269Arg)

ENG:endoglin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_001114753.3(ENG):c.806T>G (p.Met269Arg)
  • NC_000009.12:g.127825241A>C
  • NG_009551.1:g.34528T>G
  • NM_000118.3:c.806T>G
  • NM_001114753.3:c.806T>GMANE SELECT
  • NM_001278138.2:c.260T>G
  • NP_000109.1:p.Met269Arg
  • NP_001108225.1:p.Met269Arg
  • NP_001265067.1:p.Met87Arg
  • LRG_589t1:c.806T>G
  • LRG_589:g.34528T>G
  • LRG_589p1:p.Met269Arg
  • NC_000009.11:g.130587520A>C
Protein change:
dbSNP: rs752331196
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000118.3:c.806T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001114753.3:c.806T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001278138.2:c.260T>G - missense variant - [Sequence Ontology: SO:0001583]


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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV001377984Invitaecriteria provided, single submitter
(Sep 17, 2020)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

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



Update on molecular diagnosis of hereditary hemorrhagic telangiectasia.

Richards-Yutz J, Grant K, Chao EC, Walther SE, Ganguly A.

Hum Genet. 2010 Jul;128(1):61-77. doi: 10.1007/s00439-010-0825-4. Epub 2010 Apr 23.

PubMed [citation]

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

Details of each submission

From Invitae, SCV001377984.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)


This sequence change replaces methionine with arginine at codon 269 of the ENG protein (p.Met269Arg). The methionine residue is weakly conserved and there is a moderate physicochemical difference between methionine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with hereditary hemorrhagic telangiectasia (PMID: 20414677, Invitae). ClinVar contains an entry for this variant (Variation ID: 937612). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the p.Met269 amino acid residue in ENG. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Jan 8, 2022

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