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NM_001114753.3(ENG):c.1645T>G (p.Cys549Gly) AND Hereditary hemorrhagic telangiectasia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 2, 2023
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:
RCV003759041.1

Allele description [Variation Report for NM_001114753.3(ENG):c.1645T>G (p.Cys549Gly)]

NM_001114753.3(ENG):c.1645T>G (p.Cys549Gly)

Genes:
ENG:endoglin [Gene - OMIM - HGNC]
LOC102723566:uncharacterized LOC102723566 [Gene]
Variant type:
single nucleotide variant
Cytogenetic location:
9q34.11
Genomic location:
Preferred name:
NM_001114753.3(ENG):c.1645T>G (p.Cys549Gly)
HGVS:
  • NC_000009.12:g.127818161A>C
  • NG_009551.1:g.41608T>G
  • NM_000118.4:c.1645T>G
  • NM_001114753.3:c.1645T>GMANE SELECT
  • NM_001278138.2:c.1099T>G
  • NP_000109.1:p.Cys549Gly
  • NP_000109.1:p.Cys549Gly
  • NP_001108225.1:p.Cys549Gly
  • NP_001108225.1:p.Cys549Gly
  • NP_001265067.1:p.Cys367Gly
  • LRG_589t1:c.1645T>G
  • LRG_589t2:c.1645T>G
  • LRG_589:g.41608T>G
  • LRG_589p1:p.Cys549Gly
  • LRG_589p2:p.Cys549Gly
  • NC_000009.11:g.130580440A>C
  • NM_000118.3:c.1645T>G
  • NM_001114753.2:c.1645T>G
Protein change:
C367G
Links:
dbSNP: rs1830376644
NCBI 1000 Genomes Browser:
rs1830376644
Molecular consequence:
  • NM_000118.4:c.1645T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001114753.3:c.1645T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001278138.2:c.1099T>G - 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
SCV004462047Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(May 2, 2023)
germlineclinical testing

PubMed (3)
[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

Molecular diagnosis in hereditary hemorrhagic telangiectasia: findings in a series tested simultaneously by sequencing and deletion/duplication analysis.

McDonald J, Damjanovich K, Millson A, Wooderchak W, Chibuk JM, Stevenson DA, Gedge F, Bayrak-Toydemir P.

Clin Genet. 2011 Apr;79(4):335-44. doi: 10.1111/j.1399-0004.2010.01596.x. Epub 2010 Dec 16.

PubMed [citation]
PMID:
21158752
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV004462047.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Cys549 amino acid residue in ENG. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20414677, 21158752; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 995686). This missense change has been observed in individual(s) with hereditary hemorrhagic telangiectasia (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 549 of the ENG protein (p.Cys549Gly).

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

Last Updated: Feb 28, 2024