NM_001114753.3(ENG):c.1419C>G (p.Ser473Arg) AND Hereditary hemorrhagic telangiectasia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 3, 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:: RCV002568459.3

Allele description [Variation Report for NM_001114753.3(ENG):c.1419C>G (p.Ser473Arg)]

NM_001114753.3(ENG):c.1419C>G (p.Ser473Arg)

Genes:

ENG:endoglin [Gene - OMIM - HGNC]
LOC102723566:uncharacterized LOC102723566 [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.11

Genomic location:

Preferred name:

NM_001114753.3(ENG):c.1419C>G (p.Ser473Arg)

HGVS:

NC_000009.12:g.127818725G>C
NG_009551.1:g.41044C>G
NM_000118.4:c.1419C>G
NM_001114753.3:c.1419C>GMANE SELECT
NM_001278138.2:c.873C>G
NP_000109.1:p.Ser473Arg
NP_000109.1:p.Ser473Arg
NP_001108225.1:p.Ser473Arg
NP_001108225.1:p.Ser473Arg
NP_001265067.1:p.Ser291Arg
LRG_589t1:c.1419C>G
LRG_589t2:c.1419C>G
LRG_589:g.41044C>G
LRG_589p1:p.Ser473Arg
LRG_589p2:p.Ser473Arg
NC_000009.11:g.130581004G>C
NM_000118.2:c.1419C>G
NM_000118.3:c.1419C>G
NM_001114753.2:c.1419C>G

Protein change:

S291R

Links:

dbSNP: rs561818608

NCBI 1000 Genomes Browser:

rs561818608

Molecular consequence:

NM_000118.4:c.1419C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001114753.3:c.1419C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001278138.2:c.873C>G - 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
SCV003259087	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 3, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29650961, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003259087

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 3, 2022)

germline

clinical testing

PubMed (2)
[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

Identification of rare sequence variation underlying heritable pulmonary arterial hypertension.

Gräf S, Haimel M, Bleda M, Hadinnapola C, Southgate L, Li W, Hodgson J, Liu B, Salmon RM, Southwood M, Machado RD, Martin JM, Treacy CM, Yates K, Daugherty LC, Shamardina O, Whitehorn D, Holden S, Aldred M, Bogaard HJ, Church C, Coghlan G, et al.

Nat Commun. 2018 Apr 12;9(1):1416. doi: 10.1038/s41467-018-03672-4.

PubMed [citation]

PMID:: 29650961
PMCID:: PMC5897357

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003259087.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 not expected to disrupt ENG protein function. ClinVar contains an entry for this variant (Variation ID: 1204723). This missense change has been observed in individual(s) with pulmonary arterial hypertension (PMID: 29650961). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 473 of the ENG protein (p.Ser473Arg).

#	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: Sep 29, 2024

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