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NM_000118.3(ENG):c.1586G>A (p.Arg529His)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(2);Pathogenic(1);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
4 (Most recent: Jan 7, 2021)
Last evaluated:
Aug 5, 2020
Accession:
VCV000213212.5
Variation ID:
213212
Description:
single nucleotide variant
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NM_000118.3(ENG):c.1586G>A (p.Arg529His)

Allele ID
209945
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
9q34.11
Genomic location
9: 127818220 (GRCh38) GRCh38 UCSC
9: 130580499 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000009.11:g.130580499C>T
NC_000009.12:g.127818220C>T
NM_001278138.1:c.1040G>A NP_001265067.1:p.Arg347His missense
... more HGVS
Protein change
R529H, R347H
Other names
p.R529H:CGC>CAC
Canonical SPDI
NC_000009.12:127818219:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00000
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Links
ClinGen: CA321073
UniProtKB: P17813#VAR_070299
dbSNP: rs863223538
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 1 criteria provided, single submitter May 16, 2017 RCV000229345.4
Likely pathogenic 1 criteria provided, single submitter Aug 5, 2020 RCV000791433.3
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Mar 23, 2018 RCV000755259.2
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
ENG Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
588 877
LOC102723566 - - - GRCh38 - 265

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(May 16, 2017)
criteria provided, single submitter
Method: clinical testing
Hereditary hemorrhagic telangiectasia type 1
Allele origin: germline
Center of Genomic medicine, Geneva,University Hospital of Geneva
Accession: SCV000590887.1
Submitted: (Jul 06, 2017)
Evidence details
Pathogenic
(Mar 23, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories
Accession: SCV000603461.2
Submitted: (Oct 10, 2018)
Evidence details
Comment:
The ENG c.1586G>A; p.Arg529His variant (rs863223538) has been reported in the literature in individuals with symptoms of HHT (Bossler 2006, Gedge 2007, Nishida 2012). The … (more)
Uncertain significance
(Mar 23, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000250085.13
Submitted: (Jan 29, 2019)
Evidence details
Comment:
The R529H variant in the ENG gene has been reported multiple times in association with HHT (Bossler et al., 2006; Gedge et al., 2007; Bayrak-Toydemir … (more)
Likely pathogenic
(Aug 05, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary hemorrhagic telangiectasia
Allele origin: germline
Invitae
Accession: SCV000283528.6
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (5)
Comment:
This sequence change replaces arginine with histidine at codon 529 of the ENG protein (p.Arg529His). The arginine residue is highly conserved and there is a … (more)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Brain arteriovenous malformations associated with hereditary hemorrhagic telangiectasia: gene-phenotype correlations. Nishida T American journal of medical genetics. Part A 2012 PMID: 22991266
Likelihood ratios to assess genetic evidence for clinical significance of uncertain variants: hereditary hemorrhagic telangiectasia as a model. Bayrak-Toydemir P Experimental and molecular pathology 2008 PMID: 18495117
Clinical and analytical sensitivities in hereditary hemorrhagic telangiectasia testing and a report of de novo mutations. Gedge F The Journal of molecular diagnostics : JMD 2007 PMID: 17384219
Novel mutations in ENG and ACVRL1 identified in a series of 200 individuals undergoing clinical genetic testing for hereditary hemorrhagic telangiectasia (HHT): correlation of genotype with phenotype. Bossler AD Human mutation 2006 PMID: 16752392

Text-mined citations for rs863223538...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated May 10, 2021