NM_001114753.3(ENG):c.145G>T (p.Val49Phe) AND Hereditary hemorrhagic telangiectasia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 22, 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:: RCV000693521.11

Allele description [Variation Report for NM_001114753.3(ENG):c.145G>T (p.Val49Phe)]

NM_001114753.3(ENG):c.145G>T (p.Val49Phe)

Gene:

ENG:endoglin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.11

Genomic location:

Preferred name:

NM_001114753.3(ENG):c.145G>T (p.Val49Phe)

Other names:

p.Val49Phe

HGVS:

NC_000009.12:g.127843168C>A
NG_009551.1:g.16601G>T
NM_000118.4:c.145G>T
NM_001114753.3:c.145G>TMANE SELECT
NM_001278138.2:c.-402G>T
NM_001406715.1:c.145G>T
NP_000109.1:p.Val49Phe
NP_000109.1:p.Val49Phe
NP_001108225.1:p.Val49Phe
NP_001108225.1:p.Val49Phe
NP_001393644.1:p.Val49Phe
LRG_589t1:c.145G>T
LRG_589t2:c.145G>T
LRG_589:g.16601G>T
LRG_589p1:p.Val49Phe
LRG_589p2:p.Val49Phe
NC_000009.11:g.130605447C>A
NM_000118.2:c.145G>T
NM_000118.3:c.145G>T
NM_001114753.1:c.145G>T
NM_001114753.2:c.145G>T

Protein change:

V49F

Links:

dbSNP: rs1252348200

NCBI 1000 Genomes Browser:

rs1252348200

Molecular consequence:

NM_001278138.2:c.-402G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000118.4:c.145G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001114753.3:c.145G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406715.1:c.145G>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000821392	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 22, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 22022569, 15024723, 17786384, 21158752, 22991266, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000821392

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 22, 2022)

germline

clinical testing

PubMed (6)
[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

Endoplasmic reticulum quality control is involved in the mechanism of endoglin-mediated hereditary haemorrhagic telangiectasia.

Ali BR, Ben-Rebeh I, John A, Akawi NA, Milhem RM, Al-Shehhi NA, Al-Ameri MM, Al-Shamisi SA, Al-Gazali L.

PLoS One. 2011;6(10):e26206. doi: 10.1371/journal.pone.0026206. Epub 2011 Oct 14.

PubMed [citation]

PMID:: 22022569
PMCID:: PMC3194820

Molecular screening of ALK1/ACVRL1 and ENG genes in hereditary hemorrhagic telangiectasia in France.

Lesca G, Plauchu H, Coulet F, Lefebvre S, Plessis G, Odent S, Rivière S, Leheup B, Goizet C, Carette MF, Cordier JF, Pinson S, Soubrier F, Calender A, Giraud S; French Rendu-Osler Network.

Hum Mutat. 2004 Apr;23(4):289-99.

PubMed [citation]

PMID:: 15024723

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000821392.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects ENG function (PMID: 22022569). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ENG protein function. ClinVar contains an entry for this variant (Variation ID: 572196). This missense change has been observed in individuals with hereditary hemorrhagic telangiectasia (PMID: 15024723, 17786384, 21158752, 22991266). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 49 of the ENG protein (p.Val49Phe).

#	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: Nov 30, 2024

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