NM_001114753.3(ENG):c.838A>T (p.Lys280Ter) AND Hereditary hemorrhagic telangiectasia type 1

Clinical significance:Pathogenic (Last evaluated: Feb 21, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001001118.1

Allele description [Variation Report for NM_001114753.3(ENG):c.838A>T (p.Lys280Ter)]

NM_001114753.3(ENG):c.838A>T (p.Lys280Ter)

Gene:
ENG:endoglin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q34.11
Genomic location:
Preferred name:
NM_001114753.3(ENG):c.838A>T (p.Lys280Ter)
HGVS:
  • NC_000009.12:g.127824953T>A
  • NG_009551.1:g.34816A>T
  • NM_000118.3:c.838A>T
  • NM_001114753.3:c.838A>TMANE SELECT
  • NM_001278138.2:c.292A>T
  • NP_000109.1:p.Lys280Ter
  • NP_001108225.1:p.Lys280Ter
  • NP_001265067.1:p.Lys98Ter
  • LRG_589t1:c.838A>T
  • LRG_589:g.34816A>T
  • LRG_589p1:p.Lys280Ter
  • NC_000009.11:g.130587232T>A
  • NC_000009.11:g.130587232T>A
Protein change:
K280*
Links:
dbSNP: rs1588581497
NCBI 1000 Genomes Browser:
rs1588581497
Molecular consequence:
  • NM_000118.3:c.838A>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001114753.3:c.838A>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001278138.2:c.292A>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV001158257ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratoriescriteria provided, single submitter
Pathogenic
(Feb 21, 2019)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories, SCV001158257.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The ENG c.838A>T; p.Lys280Ter variant, to our knowledge, is not reported in the medical literature or gene-specific databases. This variant is also absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. ENG loss-of-function is an established mechanism of disease, and truncating variants downstream of p.Lys280Ter are reported in individuals with symptoms or diagnoses of hereditary hemorrhagic telangiectasia and are considered pathogenic (Lesca 2004, McDonald 2011). Based on available information, the p.Lys280Ter variant is considered to be pathogenic. References: Lesca G et al. Molecular screening of ALK1/ACVRL1 and ENG genes in hereditary hemorrhagic telangiectasia in France. Hum Mutat. 2004 Apr;23(4):289-99. McDonald J et al. Molecular diagnosis in hereditary hemorrhagic telangiectasia: findings in a series tested simultaneously by sequencing and deletion/duplication analysis. Clin Genet. 2011 Apr;79(4):335-44.

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

Last Updated: Oct 25, 2021

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