NM_001114753.3(ENG):c.68G>C (p.Ser23Thr) AND Hereditary hemorrhagic telangiectasia

Clinical significance:Uncertain significance (Last evaluated: Jul 24, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_001114753.3(ENG):c.68G>C (p.Ser23Thr)]

NM_001114753.3(ENG):c.68G>C (p.Ser23Thr)

ENG:endoglin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_001114753.3(ENG):c.68G>C (p.Ser23Thr)
  • NC_000009.12:g.127843245C>G
  • NG_009551.1:g.16524G>C
  • NM_000118.3:c.68G>C
  • NM_000118.3:c.68G>C
  • NM_001114753.3:c.68G>CMANE SELECT
  • NM_001278138.2:c.-479G>C
  • NP_000109.1:p.Ser23Thr
  • NP_000109.1:p.Ser23Thr
  • NP_001108225.1:p.Ser23Thr
  • LRG_589t1:c.68G>C
  • LRG_589t1:c.68G>C
  • LRG_589:g.16524G>C
  • LRG_589p1:p.Ser23Thr
  • LRG_589p1:p.Ser23Thr
  • NC_000009.11:g.130605524C>G
  • NC_000009.11:g.130605524C>G
Protein change:
Molecular consequence:
  • NM_001278138.2:c.-479G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000118.3:c.68G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001114753.3:c.68G>C - missense variant - [Sequence Ontology: SO:0001583]


Hereditary hemorrhagic telangiectasia (HHT)
Osler Weber Rendu syndrome; ORW disease; Osler-Rendu-Weber disease; See all synonyms [MedGen]
MONDO: MONDO:0019180; MedGen: C0039445; OMIM: PS187300

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV001229004Invitaecriteria provided, single submitter
Uncertain significance
(Jul 24, 2020)
germlineclinical testing

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

Summary from all submissions

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



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]

Details of each submission

From Invitae, SCV001229004.2

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


This sequence change replaces serine with threonine at codon 23 of the ENG protein (p.Ser23Thr). The serine residue is weakly conserved and there is a small physicochemical difference between serine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ENG-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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

Last Updated: Oct 24, 2021

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