NM_000118.3(ENG):c.1088G>C (p.Cys363Ser) AND Hereditary hemorrhagic telangiectasia

Clinical significance:Likely pathogenic (Last evaluated: Nov 30, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000819037.1

Allele description [Variation Report for NM_000118.3(ENG):c.1088G>C (p.Cys363Ser)]

NM_000118.3(ENG):c.1088G>C (p.Cys363Ser)

Gene:
ENG:endoglin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q34.11
Genomic location:
Preferred name:
NM_000118.3(ENG):c.1088G>C (p.Cys363Ser)
HGVS:
  • NC_000009.12:g.127824350C>G
  • NG_009551.1:g.35419G>C
  • NM_000118.3:c.1088G>C
  • NM_001114753.2:c.1088G>C
  • NM_001278138.1:c.542G>C
  • NP_000109.1:p.Cys363Ser
  • NP_001108225.1:p.Cys363Ser
  • NP_001265067.1:p.Cys181Ser
  • LRG_589t1:c.1088G>C
  • LRG_589t2:c.1088G>C
  • LRG_589:g.35419G>C
  • LRG_589p1:p.Cys363Ser
  • LRG_589p2:p.Cys363Ser
  • NC_000009.11:g.130586629C>G
Protein change:
C181S
Links:
dbSNP: rs1588580782
NCBI 1000 Genomes Browser:
rs1588580782
Molecular consequence:
  • NM_000118.3:c.1088G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001114753.2:c.1088G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001278138.1:c.542G>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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000959678Invitaecriteria provided, single submitter
Likely pathogenic
(Nov 30, 2018)
germlineclinical testing

PubMed (6)
[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

Hypogonadotropic hypogonadism associated with hereditary hemorrhagic telangiectasia [corrected].

Scarano V, De Santis D, Suppressa P, Lastella P, Lenato GM, Triggiani V, SabbĂ  C.

Case Rep Endocrinol. 2013;2013:465376. doi: 10.1155/2013/465376. Epub 2013 Apr 4. Erratum in: Case Rep Endocrinol. 2013;2013:520284. Scarano, Valentina (2) Valentina, Scarano (3) De Santis, Daniele (4) Daniele, De Santis (5) Suppressa, Patrizia (6) Patrizia, Suppressa (7) Patrizia, Lastella [corrected to Lastella, Patrizia]; Mariano, Lenato Gennaro [corrected to Lenato, Gennaro Mariano]. Case Rep Endocrinol. 2013;2013:520284.

PubMed [citation]
PMID:
23710379
PMCID:
PMC3638540
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000959678.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change replaces cysteine with serine at codon 363 of the ENG protein (p.Cys363Ser). The cysteine residue is moderately conserved and there is a moderate physicochemical difference between cysteine and serine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in several individuals with clinical features of hereditary hemorrhagic telangiectasia (HHT) (PMID: 24196379, 17384219, 22991266, 23710379). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Cys363 amino acid residue in ENG. Other variant(s) that disrupt this residue have been observed in individuals with ENG-related conditions (PMID: 11440987), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Oct 7, 2021

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