NM_001114753.3(ENG):c.1771G>A (p.Ala591Thr) AND Hereditary hemorrhagic telangiectasia

Clinical significance:Uncertain significance (Last evaluated: Oct 30, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001345954.1

Allele description [Variation Report for NM_001114753.3(ENG):c.1771G>A (p.Ala591Thr)]

NM_001114753.3(ENG):c.1771G>A (p.Ala591Thr)

Gene:
ENG:endoglin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q34.11
Genomic location:
Preferred name:
NM_001114753.3(ENG):c.1771G>A (p.Ala591Thr)
HGVS:
  • NC_000009.12:g.127816024C>T
  • NG_009551.1:g.43745G>A
  • NG_023245.1:g.18150C>T
  • NM_000118.3:c.1771G>A
  • NM_001114753.3:c.1771G>AMANE SELECT
  • NM_001278138.2:c.1225G>A
  • NP_000109.1:p.Ala591Thr
  • NP_001108225.1:p.Ala591Thr
  • NP_001265067.1:p.Ala409Thr
  • LRG_589t1:c.1771G>A
  • LRG_589:g.43745G>A
  • LRG_589p1:p.Ala591Thr
  • NC_000009.11:g.130578303C>T
Protein change:
A409T
Molecular consequence:
  • NM_000118.3:c.1771G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001114753.3:c.1771G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001278138.2:c.1225G>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
SCV001540107Invitaecriteria provided, single submitter
Uncertain significance
(Oct 30, 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

Mutation analysis of "Endoglin" and "Activin receptor-like kinase" genes in German patients with hereditary hemorrhagic telangiectasia and the value of rapid genotyping using an allele-specific PCR-technique.

Sadick H, Hage J, Goessler U, Stern-Straeter J, Riedel F, Hoermann K, Bugert P.

BMC Med Genet. 2009 Jun 9;10:53. doi: 10.1186/1471-2350-10-53.

PubMed [citation]
PMID:
19508727
PMCID:
PMC2701415

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, SCV001540107.1

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

Description

This sequence change replaces alanine with threonine at codon 591 of the ENG protein (p.Ala591Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs200080694, ExAC 0.01%). This variant has been observed in individual(s) with clinical features of hereditary hemorrhagic telangiectasia (PMID: 19508727). 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 not expected to disrupt ENG protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 7, 2021

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