NM_001114753.3(ENG):c.-8_8del (p.Met1fs) AND Hereditary hemorrhagic telangiectasia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 5, 2022
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:: RCV000814719.8

Allele description [Variation Report for NM_001114753.3(ENG):c.-8_8del (p.Met1fs)]

NM_001114753.3(ENG):c.-8_8del (p.Met1fs)

Gene:

ENG:endoglin [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

9q34.11

Genomic location:

Preferred name:

NM_001114753.3(ENG):c.-8_8del (p.Met1fs)

HGVS:

NC_000009.12:g.127854350_127854365del
NG_009551.1:g.5406_5421del
NM_000118.4:c.-10_6del16
NM_001114753.3:c.-8_8delMANE SELECT
NM_001406715.1:c.-10_6del16
NP_000109.1:p.Met(?_1)_Asp2(?)
NP_000109.1:p.Met1fs
NP_001108225.1:p.Met(?_1)_Asp2(?)
NP_001108225.1:p.Met1fs
NP_001393644.1:p.Met(?_1)_Asp2(?)
LRG_589t1:c.-8_8del
LRG_589t2:c.-10_6del16
LRG_589:g.5406_5421del
LRG_589p1:p.Met1fs
LRG_589p2:p.Met(?_1)_Asp2(?)
NC_000009.11:g.130616627_130616642del
NC_000009.11:g.130616629_130616644del
NM_000118.3:c.-8_8del
NM_001114753.2:c.-10_6del16

Protein change:

M1fs

Links:

dbSNP: rs1588604603

NCBI 1000 Genomes Browser:

rs1588604603

Molecular consequence:

NM_000118.4:c.-10_6del16 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001114753.3:c.-8_8del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406715.1:c.-10_6del16 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001114753.3:c.-8_8del - initiator_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

Recent activity

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cystatin-A [Equus caballus]
cystatin-A [Equus caballus]
gi|338716231|ref|XP_003363423.1|

Protein
Rattus norvegicus strain mixed contig_43952.1, whole genome shotgun sequence
Rattus norvegicus strain mixed contig_43952.1, whole genome shotgun sequence
gi|661387523|gb|AABR07043107.1||gnl AABR07|contig_43952.1

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000955141	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 5, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 12920067, 15517393, 16429404, 21158752, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000955141

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 5, 2022)

germline

clinical testing

PubMed (5)
[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: 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

Hereditary hemorrhagic telangiectasia: ENG and ALK-1 mutations in Dutch patients.

Letteboer TG, Zewald RA, Kamping EJ, de Haas G, Mager JJ, Snijder RJ, Lindhout D, Hennekam FA, Westermann CJ, Ploos van Amstel JK.

Hum Genet. 2005 Jan;116(1-2):8-16. Epub 2004 Oct 23.

PubMed [citation]

PMID:: 15517393

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000955141.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 657994). Disruption of the initiator codon has been observed in individuals with hereditary hemorrhagic telangiectasia (PMID: 12920067, 15517393, 16429404, 21158752). This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the ENG mRNA. The next in-frame methionine is located at codon 183.

#	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: Feb 14, 2024

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