NM_001114753.3(ENG):c.1121_1124del (p.Lys374fs) AND Hereditary hemorrhagic telangiectasia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 17, 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:: RCV000530282.11

Allele description [Variation Report for NM_001114753.3(ENG):c.1121_1124del (p.Lys374fs)]

NM_001114753.3(ENG):c.1121_1124del (p.Lys374fs)

Gene:

ENG:endoglin [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

9q34.11

Genomic location:

Preferred name:

NM_001114753.3(ENG):c.1121_1124del (p.Lys374fs)

HGVS:

NC_000009.12:g.127824315CTTT[1]
NG_009551.1:g.35448AAGA[1]
NM_000118.4:c.1116_1119AAAG[1]
NM_001114753.3:c.1121_1124delMANE SELECT
NM_001278138.2:c.575_578del
NM_001406715.1:c.1116_1119AAAG[1]
NP_000109.1:p.Lys374Serfs
NP_000109.1:p.Lys374fs
NP_001108225.1:p.Lys374Serfs
NP_001108225.1:p.Lys374fs
NP_001265067.1:p.Lys192fs
NP_001393644.1:p.Lys374Serfs
LRG_589t1:c.1121_1124del
LRG_589t2:c.1116_1119AAAG[1]
LRG_589:g.35448AAGA[1]
LRG_589p1:p.Lys374fs
LRG_589p2:p.Lys374Serfs
NC_000009.11:g.130586593_130586596del
NC_000009.11:g.130586594CTTT[1]
NM_000118.2:c.1121_1124delAAGA
NM_000118.3:c.1121_1124del
NM_000118.3:c.1121_1124delAAGA
NM_001114753.1:c.1121_1124delAAGA
NM_001114753.2:c.1116_1119AAAG[1]

Protein change:

K192fs

Links:

dbSNP: rs1064793734

NCBI 1000 Genomes Browser:

rs1064793734

Molecular consequence:

NM_000118.4:c.1116_1119AAAG[1] - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001114753.3:c.1121_1124del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001278138.2:c.575_578del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406715.1:c.1116_1119AAAG[1] - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000629543	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 17, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15879500, 11793473, 20501893, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000629543

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 17, 2023)

germline

clinical testing

PubMed (4)
[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

Genetic epidemiology of hereditary hemorrhagic telangiectasia in a local community in the northern part of Japan.

Dakeishi M, Shioya T, Wada Y, Shindo T, Otaka K, Manabe M, Nozaki J, Inoue S, Koizumi A.

Hum Mutat. 2002 Feb;19(2):140-8.

PubMed [citation]

PMID:: 11793473

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000629543.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant is also known as c.1120_1123delAAAG. This sequence change creates a premature translational stop signal (p.Lys374Serfs*6) 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 premature translational stop signal has been observed in individuals with hereditary hemorrhagic telangiectasia (PMID: 11793473, 20501893; Invitae). ClinVar contains an entry for this variant (Variation ID: 419225). 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

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