NM_001114753.3(ENG):c.688G>A (p.Gly230Arg) AND Hereditary hemorrhagic telangiectasia

Clinical significance:Uncertain significance (Last evaluated: Mar 6, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001350992.1

Allele description [Variation Report for NM_001114753.3(ENG):c.688G>A (p.Gly230Arg)]

NM_001114753.3(ENG):c.688G>A (p.Gly230Arg)

Gene:
ENG:endoglin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q34.11
Genomic location:
Preferred name:
NM_001114753.3(ENG):c.688G>A (p.Gly230Arg)
HGVS:
  • NC_000009.12:g.127825696C>T
  • NG_009551.1:g.34073G>A
  • NM_000118.3:c.688G>A
  • NM_001114753.3:c.688G>AMANE SELECT
  • NM_001278138.2:c.142G>A
  • NP_000109.1:p.Gly230Arg
  • NP_001108225.1:p.Gly230Arg
  • NP_001265067.1:p.Gly48Arg
  • LRG_589t1:c.688G>A
  • LRG_589:g.34073G>A
  • LRG_589p1:p.Gly230Arg
  • NC_000009.11:g.130587975C>T
Protein change:
G230R
Molecular consequence:
  • NM_000118.3:c.688G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001114753.3:c.688G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001278138.2:c.142G>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
SCV001545423Invitaecriteria provided, single submitter
Uncertain significance
(Mar 6, 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

Functional analysis of endoglin mutations from hereditary hemorrhagic telangiectasia type 1 patients reveals different mechanisms for endoglin loss of function.

Mallet C, Lamribet K, Giraud S, Dupuis-Girod S, Feige JJ, Bailly S, Tillet E.

Hum Mol Genet. 2015 Feb 15;24(4):1142-54. doi: 10.1093/hmg/ddu531. Epub 2014 Oct 13.

PubMed [citation]
PMID:
25312062

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, SCV001545423.1

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

Description

This sequence change replaces glycine with arginine at codon 230 of the ENG protein (p.Gly230Arg). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs546671241, ExAC 0.03%). This variant has been observed in individual(s) with nosebleed (PMID: 25312062). This variant has been reported not to substantially affect ENG protein function (PMID: 25312062). 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 7, 2021

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