NM_000118.3(ENG):c.1080_1083del (p.Thr361fs) AND Hereditary hemorrhagic telangiectasia type 1

Clinical significance:Pathogenic (Last evaluated: Jan 1, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000234034.3

Allele description [Variation Report for NM_000118.3(ENG):c.1080_1083del (p.Thr361fs)]

NM_000118.3(ENG):c.1080_1083del (p.Thr361fs)

Gene:
ENG:endoglin [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
9q34.11
Genomic location:
Preferred name:
NM_000118.3(ENG):c.1080_1083del (p.Thr361fs)
HGVS:
  • NC_000009.12:g.127824357_127824360del
  • NG_009551.1:g.35411_35414del
  • NM_000118.3:c.1080_1083del
  • NM_001114753.2:c.1080_1083del
  • NM_001278138.1:c.534_537del
  • NP_000109.1:p.Thr361fs
  • NP_001108225.1:p.Thr361fs
  • NP_001265067.1:p.Thr179fs
  • LRG_589t1:c.1080_1083del
  • LRG_589t2:c.1080_1083del
  • LRG_589:g.35411_35414del
  • LRG_589p1:p.Thr361fs
  • LRG_589p2:p.Thr361fs
  • NC_000009.11:g.130586636_130586639del
  • NM_000118.2:c.1080_1083delGACA
  • NM_000118.3:c.1080_1083delGACA
  • NM_001114753.2:c.1080_1083delGACA
  • p.T361Sfs*7
  • p.Thr361Serfs*7
Protein change:
T179fs
Links:
dbSNP: rs863223540
NCBI 1000 Genomes Browser:
rs863223540
Molecular consequence:
  • NM_000118.3:c.1080_1083del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001114753.2:c.1080_1083del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001278138.1:c.534_537del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Hereditary hemorrhagic telangiectasia type 1 (HHT1)
Synonyms:
Osler Weber Rendu syndrome type 1
Identifiers:
MONDO: MONDO:0008535; MedGen: C4551861; Orphanet: 774; OMIM: 187300

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000283521Invitaecriteria provided, single submitter
Pathogenic
(Apr 8, 2017)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001439428NIHR Bioresource Rare Diseases, University of Cambridgecriteria provided, single submitter
Pathogenic
(Jan 1, 2018)
unknownresearch

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
not providedunknownyes3not providednot providednot providednot providedresearch

Citations

PubMed

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

Mutational and phenotypic characterization of hereditary hemorrhagic telangiectasia.

Shovlin CL, Simeoni I, Downes K, Frazer ZC, Megy K, Bernabeu-Herrero ME, Shurr A, Brimley J, Patel D, Kell L, Stephens J, Turbin IG, Aldred MA, Penkett CJ, Ouwehand WH, Jovine L, Turro E.

Blood. 2020 Oct 22;136(17):1907-1918. doi: 10.1182/blood.2019004560.

PubMed [citation]
PMID:
32573726
PMCID:
PMC7717479
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000283521.2

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

Description

This sequence change deletes 4 nucleotide from exon 8 of the ENG mRNA (c.1080_1083delGACA), causing a frameshift at codon 361. This creates a premature translational stop signal (p.Thr361Serfs*7) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in ENG are known to be pathogenic. This particular truncation has been reported in the literature in multiple individuals affected with hereditary hemorrhagic telangiectasia (PMID: 9554745, 22991266, 16542389, 17786384, 21158752). For these reasons, this variant has been classified as Pathogenic.

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

From NIHR Bioresource Rare Diseases, University of Cambridge, SCV001439428.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedresearch PubMed (2)

Description

PVS1+PM2+PP4

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot provided3not providednot providednot provided

Last Updated: Jun 14, 2021

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