NM_001114753.3(ENG):c.841A>G (p.Ile281Val) AND Hereditary hemorrhagic telangiectasia

Clinical significance:Uncertain significance (Last evaluated: Oct 1, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001219675.2

Allele description [Variation Report for NM_001114753.3(ENG):c.841A>G (p.Ile281Val)]

NM_001114753.3(ENG):c.841A>G (p.Ile281Val)

Gene:
ENG:endoglin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q34.11
Genomic location:
Preferred name:
NM_001114753.3(ENG):c.841A>G (p.Ile281Val)
HGVS:
  • NC_000009.12:g.127824950T>C
  • NG_009551.1:g.34819A>G
  • NM_000118.3:c.841A>G
  • NM_000118.3:c.841A>G
  • NM_001114753.3:c.841A>GMANE SELECT
  • NM_001278138.2:c.295A>G
  • NP_000109.1:p.Ile281Val
  • NP_000109.1:p.Ile281Val
  • NP_001108225.1:p.Ile281Val
  • NP_001265067.1:p.Ile99Val
  • LRG_589t1:c.841A>G
  • LRG_589:g.34819A>G
  • LRG_589p1:p.Ile281Val
  • NC_000009.11:g.130587229T>C
  • NC_000009.11:g.130587229T>C
Protein change:
I281V
Molecular consequence:
  • NM_000118.3:c.841A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001114753.3:c.841A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001278138.2:c.295A>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
SCV001391625Invitaecriteria provided, single submitter
Uncertain significance
(Oct 1, 2020)
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

Variant analysis in Chinese families with hereditary hemorrhagic telangiectasia.

Zhao Y, Zhang Y, Wang X, Zhang L.

Mol Genet Genomic Med. 2019 Sep;7(9):e893. doi: 10.1002/mgg3.893. Epub 2019 Aug 10.

PubMed [citation]
PMID:
31400083
PMCID:
PMC6732279

Germline BMP9 mutation causes idiopathic pulmonary arterial hypertension.

Wang XJ, Lian TY, Jiang X, Liu SF, Li SQ, Jiang R, Wu WH, Ye J, Cheng CY, Du Y, Xu XQ, Wu Y, Peng FH, Sun K, Mao YM, Yu H, Liang C, Shyy JY, Zhang SY, Zhang X, Jing ZC.

Eur Respir J. 2019 Mar 14;53(3). doi:pii: 1801609. 10.1183/13993003.01609-2018. Print 2019 Mar.

PubMed [citation]
PMID:
30578397
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001391625.2

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

Description

This sequence change replaces isoleucine with valine at codon 281 of the ENG protein (p.Ile281Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs764640510, ExAC 0.01%). This variant has been observed in individual(s) with hereditary hemorrhagic telangiectasia (PMID: 31400083) and idiopathic pulmonary arterial hypertension (PMID: 30578397). This variant is also known as c.A295G (p.I99V). 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: Tolerated; 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. 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 24, 2021

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