NM_001114753.3(ENG):c.1003C>T (p.Gln335Ter) AND Hereditary hemorrhagic telangiectasia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 22, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003096932.2

Allele description [Variation Report for NM_001114753.3(ENG):c.1003C>T (p.Gln335Ter)]

NM_001114753.3(ENG):c.1003C>T (p.Gln335Ter)

Gene:

ENG:endoglin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.11

Genomic location:

Preferred name:

NM_001114753.3(ENG):c.1003C>T (p.Gln335Ter)

HGVS:

NC_000009.12:g.127824435G>A
NG_009551.1:g.35334C>T
NM_000118.4:c.1003C>T
NM_001114753.3:c.1003C>TMANE SELECT
NM_001278138.2:c.457C>T
NM_001406715.1:c.1003C>T
NP_000109.1:p.Gln335Ter
NP_000109.1:p.Gln335Ter
NP_001108225.1:p.Gln335Ter
NP_001108225.1:p.Gln335Ter
NP_001265067.1:p.Gln153Ter
NP_001393644.1:p.Gln335Ter
LRG_589t1:c.1003C>T
LRG_589t2:c.1003C>T
LRG_589:g.35334C>T
LRG_589p1:p.Gln335Ter
LRG_589p2:p.Gln335Ter
NC_000009.11:g.130586714G>A
NM_000118.3:c.1003C>T
NM_001114753.1:c.1003C>T
NM_001114753.2:c.1003C>T

Protein change:

Q153*

Molecular consequence:

NM_000118.4:c.1003C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001114753.3:c.1003C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001278138.2:c.457C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406715.1:c.1003C>T - nonsense - [Sequence Ontology: SO:0001587]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003347551	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 22, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 15879500, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003347551

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 22, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Hereditary haemorrhagic telangiectasia: current views on genetics and mechanisms of disease.

Abdalla SA, Letarte M.

J Med Genet. 2006 Feb;43(2):97-110. Epub 2005 May 6. Review.

PubMed [citation]

PMID:: 15879500
PMCID:: PMC2603035

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, SCV003347551.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Gln335*) in the ENG gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ENG are known to be pathogenic (PMID: 15879500). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ENG-related conditions. ClinVar contains an entry for this variant (Variation ID: 1775208). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 1, 2024

ClinVar

Relating variation to medicine