NM_001114753.3(ENG):c.727G>A (p.Ala243Thr) AND Hereditary hemorrhagic telangiectasia

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 25, 2020
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:: RCV001370738.1

Allele description

NM_001114753.3(ENG):c.727G>A (p.Ala243Thr)

Gene:

ENG:endoglin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.11

Genomic location:

Preferred name:

NM_001114753.3(ENG):c.727G>A (p.Ala243Thr)

HGVS:

NC_000009.12:g.127825320C>T
NG_009551.1:g.34449G>A
NM_000118.3:c.727G>A
NM_001114753.3:c.727G>AMANE SELECT
NM_001278138.2:c.181G>A
NP_000109.1:p.Ala243Thr
NP_001108225.1:p.Ala243Thr
NP_001265067.1:p.Ala61Thr
LRG_589t1:c.727G>A
LRG_589:g.34449G>A
LRG_589p1:p.Ala243Thr
NC_000009.11:g.130587599C>T

Protein change:

A243T

Links:

dbSNP: rs761827492

NCBI 1000 Genomes Browser:

rs761827492

Molecular consequence:

NM_000118.3:c.727G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001114753.3:c.727G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001278138.2:c.181G>A - 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
SCV001567267	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 25, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001567267

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 25, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV001567267.1

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

Description

This sequence change replaces alanine with threonine at codon 243 of the ENG protein (p.Ala243Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs761827492, ExAC 0.02%). This variant has not been reported in the literature in individuals with ENG-related conditions. ClinVar contains an entry for this variant (Variation ID: 439648). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Apr 23, 2022

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