NM_001114753.3(ENG):c.899T>C (p.Leu300Pro) AND Hereditary hemorrhagic telangiectasia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 2, 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:: RCV003594026.1

Allele description [Variation Report for NM_001114753.3(ENG):c.899T>C (p.Leu300Pro)]

NM_001114753.3(ENG):c.899T>C (p.Leu300Pro)

Gene:

ENG:endoglin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.11

Genomic location:

Preferred name:

NM_001114753.3(ENG):c.899T>C (p.Leu300Pro)

HGVS:

NC_000009.12:g.127824892A>G
NG_009551.1:g.34877T>C
NM_000118.4:c.899T>C
NM_001114753.3:c.899T>CMANE SELECT
NM_001278138.2:c.353T>C
NM_001406715.1:c.899T>C
NP_000109.1:p.Leu300Pro
NP_000109.1:p.Leu300Pro
NP_001108225.1:p.Leu300Pro
NP_001108225.1:p.Leu300Pro
NP_001265067.1:p.Leu118Pro
NP_001393644.1:p.Leu300Pro
LRG_589t1:c.899T>C
LRG_589t2:c.899T>C
LRG_589:g.34877T>C
LRG_589p1:p.Leu300Pro
LRG_589p2:p.Leu300Pro
NC_000009.11:g.130587171A>G
NM_000118.2:c.899T>C
NM_000118.3:c.899T>C
NM_001114753.1:c.899T>C
NM_001114753.2:c.899T>C

Protein change:

L118P

Links:

dbSNP: rs1335718486

NCBI 1000 Genomes Browser:

rs1335718486

Molecular consequence:

NM_000118.4:c.899T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001114753.3:c.899T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001278138.2:c.353T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406715.1:c.899T>C - 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
SCV004294040	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 2, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 17384219, 18495117, 32573726, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004294040

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 2, 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

Clinical and analytical sensitivities in hereditary hemorrhagic telangiectasia testing and a report of de novo mutations.

Gedge F, McDonald J, Phansalkar A, Chou LS, Calderon F, Mao R, Lyon E, Bayrak-Toydemir P.

J Mol Diagn. 2007 Apr;9(2):258-65.

PubMed [citation]

PMID:: 17384219
PMCID:: PMC1867450

Likelihood ratios to assess genetic evidence for clinical significance of uncertain variants: hereditary hemorrhagic telangiectasia as a model.

Bayrak-Toydemir P, McDonald J, Mao R, Phansalkar A, Gedge F, Robles J, Goldgar D, Lyon E.

Exp Mol Pathol. 2008 Aug;85(1):45-9. doi: 10.1016/j.yexmp.2008.03.006. Epub 2008 Apr 8.

PubMed [citation]

PMID:: 18495117

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV004294040.1

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

Description

This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 300 of the ENG protein (p.Leu300Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with hereditary hemorrhagic telangiectasia (PMID: 17384219, 18495117, 32573726). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 618623). 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 with a positive predictive value of 80%. 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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