NM_001114753.3(ENG):c.1234T>G (p.Cys412Gly) AND Hereditary hemorrhagic telangiectasia

Clinical significance:Uncertain significance (Last evaluated: Feb 18, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001343795.1

Allele description [Variation Report for NM_001114753.3(ENG):c.1234T>G (p.Cys412Gly)]

NM_001114753.3(ENG):c.1234T>G (p.Cys412Gly)

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.1234T>G (p.Cys412Gly)
HGVS:
  • NC_000009.12:g.127819938A>C
  • NG_009551.1:g.39831T>G
  • NM_000118.3:c.1234T>G
  • NM_001114753.3:c.1234T>GMANE SELECT
  • NM_001278138.2:c.688T>G
  • NP_000109.1:p.Cys412Gly
  • NP_001108225.1:p.Cys412Gly
  • NP_001265067.1:p.Cys230Gly
  • LRG_589t1:c.1234T>G
  • LRG_589:g.39831T>G
  • LRG_589p1:p.Cys412Gly
  • NC_000009.11:g.130582217A>C
Protein change:
C230G
Molecular consequence:
  • NM_000118.3:c.1234T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001114753.3:c.1234T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001278138.2:c.688T>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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001537803Invitaecriteria provided, single submitter
Uncertain significance
(Feb 18, 2020)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Hereditary hemorrhagic telangiectasia in Japanese patients.

Komiyama M, Ishiguro T, Yamada O, Morisaki H, Morisaki T.

J Hum Genet. 2014 Jan;59(1):37-41. doi: 10.1038/jhg.2013.113. Epub 2013 Nov 7.

PubMed [citation]
PMID:
24196379

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
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001537803.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces cysteine with glycine at codon 412 of the ENG protein (p.Cys412Gly). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of hereditary hemorrhagic telangiectasia (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). This variant disrupts the p.Cys412 amino acid residue in ENG. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 24196379, 22022569, 15024723, 25312062). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 7, 2021

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