NM_001114753.3(ENG):c.806T>A (p.Met269Lys) AND Hereditary hemorrhagic telangiectasia

Clinical significance:Pathogenic (Last evaluated: Sep 15, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001381129.1

Allele description [Variation Report for NM_001114753.3(ENG):c.806T>A (p.Met269Lys)]

NM_001114753.3(ENG):c.806T>A (p.Met269Lys)

Gene:
ENG:endoglin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q34.11
Genomic location:
Preferred name:
NM_001114753.3(ENG):c.806T>A (p.Met269Lys)
HGVS:
  • NC_000009.12:g.127825241A>T
  • NG_009551.1:g.34528T>A
  • NM_000118.3:c.806T>A
  • NM_001114753.3:c.806T>AMANE SELECT
  • NM_001278138.2:c.260T>A
  • NP_000109.1:p.Met269Lys
  • NP_001108225.1:p.Met269Lys
  • NP_001265067.1:p.Met87Lys
  • LRG_589t1:c.806T>A
  • LRG_589:g.34528T>A
  • LRG_589p1:p.Met269Lys
  • NC_000009.11:g.130587520A>T
Protein change:
M269K
Molecular consequence:
  • NM_000118.3:c.806T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001114753.3:c.806T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001278138.2:c.260T>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
SCV001579382Invitaecriteria provided, single submitter
Pathogenic
(Sep 15, 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

Citations

PubMed

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]
PMID:
20414677

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]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001579382.1

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

Description

This sequence change replaces methionine with lysine at codon 269 of the ENG protein (p.Met269Lys). The methionine residue is weakly conserved and there is a moderate physicochemical difference between methionine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of hereditary hemorrhagic telangiectasia (Invitae). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ENG protein function. This variant disrupts the p.Met269 amino acid residue in ENG. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20414677, 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.

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

Last Updated: Jan 8, 2022

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