NM_000118.3(ENG):c.1311G>T (p.Arg437=) AND Hereditary hemorrhagic telangiectasia

Clinical significance:Likely pathogenic (Last evaluated: Dec 7, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000686208.2

Allele description [Variation Report for NM_000118.3(ENG):c.1311G>T (p.Arg437=)]

NM_000118.3(ENG):c.1311G>T (p.Arg437=)

Genes:
ENG:endoglin [Gene - OMIM - HGNC]
LOC102723566:uncharacterized LOC102723566 [Gene]
Variant type:
single nucleotide variant
Cytogenetic location:
9q34.11
Genomic location:
Preferred name:
NM_000118.3(ENG):c.1311G>T (p.Arg437=)
HGVS:
  • NC_000009.12:g.127819622C>A
  • NG_009551.1:g.40147G>T
  • NM_000118.3:c.1311G>T
  • NM_001114753.2:c.1311G>T
  • NM_001278138.1:c.765G>T
  • NP_000109.1:p.Arg437=
  • NP_001108225.1:p.Arg437=
  • NP_001265067.1:p.Arg255=
  • LRG_589t1:c.1311G>T
  • LRG_589t2:c.1311G>T
  • LRG_589:g.40147G>T
  • LRG_589p1:p.Arg437=
  • LRG_589p2:p.Arg437=
  • NC_000009.11:g.130581901C>A
Links:
dbSNP: rs1554809448
NCBI 1000 Genomes Browser:
rs1554809448
Molecular consequence:
  • NM_000118.3:c.1311G>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001114753.2:c.1311G>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001278138.1:c.765G>T - synonymous variant - [Sequence Ontology: SO:0001819]

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
SCV000813716Invitaecriteria provided, single submitter
Likely pathogenic
(Dec 7, 2018)
germlineclinical testing

PubMed (4)
[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 and expression analysis of the endoglin gene in hereditary hemorrhagic telangiectasia reveals null alleles.

Gallione CJ, Klaus DJ, Yeh EY, Stenzel TT, Xue Y, Anthony KB, McAllister KA, Baldwin MA, Berg JN, Lux A, Smith JD, Vary CP, Craigen WJ, Westermann CJ, Warner ML, Miller YE, Jackson CE, Guttmacher AE, Marchuk DA.

Hum Mutat. 1998;11(4):286-94.

PubMed [citation]
PMID:
9554745

Hereditary hemorrhagic telangiectasia: ENG and ALK-1 mutations in Dutch patients.

Letteboer TG, Zewald RA, Kamping EJ, de Haas G, Mager JJ, Snijder RJ, Lindhout D, Hennekam FA, Westermann CJ, Ploos van Amstel JK.

Hum Genet. 2005 Jan;116(1-2):8-16. Epub 2004 Oct 23.

PubMed [citation]
PMID:
15517393
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000813716.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change affects codon 437 of the ENG mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the ENG protein. This variant also falls at the last nucleotide of exon 10 of the ENG coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with hereditary hemorrhagic telangiectasia (PMID: 21158752, Invitae). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Two additional variants affecting this nucleotide (c.1311G>C, c.1311G>A) has been determined to be pathogenic (PMID: 9554745, 15517393). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Oct 7, 2021

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