NM_000118.3(ENG):c.-8_8del (p.Met1fs) AND Hereditary hemorrhagic telangiectasia

Clinical significance:Likely pathogenic (Last evaluated: Oct 17, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000814719.1

Allele description [Variation Report for NM_000118.3(ENG):c.-8_8del (p.Met1fs)]

NM_000118.3(ENG):c.-8_8del (p.Met1fs)

Gene:
ENG:endoglin [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
9q34.11
Genomic location:
Preferred name:
NM_000118.3(ENG):c.-8_8del (p.Met1fs)
HGVS:
  • NC_000009.12:g.127854350_127854365del
  • NG_009551.1:g.5406_5421del
  • NM_000118.3:c.-8_8del
  • NM_001114753.2:c.-8_8del
  • NP_000109.1:p.Met1fs
  • NP_001108225.1:p.Met1fs
  • LRG_589t1:c.-8_8del
  • LRG_589t2:c.-8_8del
  • LRG_589:g.5406_5421del
  • LRG_589p1:p.Met1fs
  • LRG_589p2:p.Met1fs
  • NC_000009.11:g.130616629_130616644del
Protein change:
M1fs
Links:
dbSNP: rs1588604603
NCBI 1000 Genomes Browser:
rs1588604603
Molecular consequence:
  • NM_000118.3:c.-8_8del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001114753.2:c.-8_8del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001114753.2:c.-8_8del - initiatior codon variant - [Sequence Ontology: SO:0001582]

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
SCV000955141Invitaecriteria provided, single submitter
Likely pathogenic
(Oct 17, 2018)
germlineclinical testing

PubMed (5)
[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

DHPLC-based mutation analysis of ENG and ALK-1 genes in HHT Italian population.

Lenato GM, Lastella P, Di Giacomo MC, Resta N, Suppressa P, Pasculli G, SabbĂ  C, Guanti G.

Hum Mutat. 2006 Feb;27(2):213-4.

PubMed [citation]
PMID:
16429404

Hereditary haemorrhagic telangiectasia: a questionnaire based study to delineate the different phenotypes caused by endoglin and ALK1 mutations.

Berg J, Porteous M, Reinhardt D, Gallione C, Holloway S, Umasunthar T, Lux A, McKinnon W, Marchuk D, Guttmacher A.

J Med Genet. 2003 Aug;40(8):585-90.

PubMed [citation]
PMID:
12920067
PMCID:
PMC1735540
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000955141.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change affects the initiator methionine of the ENG mRNA. The next in-frame methionine is located at codon 183. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ENG-related disease. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the disrupted amino acids is currently unknown. Several different variants (c.2T>G, c.1A>G, and c.1A>C) disrupting the initiator codon have been reported in individuals affected with hereditary hemorrhagic telangiectasia (PMID: 12920067, 21158752, 15517393, 16429404, Invitae), indicating that this residue may be critical for protein function. 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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