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NM_000020.3(ACVRL1):c.839A>G (p.His280Arg) AND Cardiovascular phenotype

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Feb 15, 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:
RCV002434870.2

Allele description [Variation Report for NM_000020.3(ACVRL1):c.839A>G (p.His280Arg)]

NM_000020.3(ACVRL1):c.839A>G (p.His280Arg)

Gene:
ACVRL1:activin A receptor like type 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q13.13
Genomic location:
Preferred name:
NM_000020.3(ACVRL1):c.839A>G (p.His280Arg)
HGVS:
  • NC_000012.12:g.51915291A>G
  • NG_009549.1:g.12874A>G
  • NM_000020.3:c.839A>GMANE SELECT
  • NM_001077401.2:c.839A>G
  • NM_001406487.1:c.839A>G
  • NM_001406488.1:c.839A>G
  • NM_001406489.1:c.839A>G
  • NM_001406490.1:c.527A>G
  • NM_001406491.1:c.527A>G
  • NM_001406492.1:c.527A>G
  • NM_001406493.1:c.527A>G
  • NM_001406494.1:c.527A>G
  • NM_001406495.1:c.275A>G
  • NP_000011.2:p.His280Arg
  • NP_000011.2:p.His280Arg
  • NP_001070869.1:p.His280Arg
  • NP_001393416.1:p.His280Arg
  • NP_001393417.1:p.His280Arg
  • NP_001393418.1:p.His280Arg
  • NP_001393419.1:p.His176Arg
  • NP_001393420.1:p.His176Arg
  • NP_001393421.1:p.His176Arg
  • NP_001393422.1:p.His176Arg
  • NP_001393423.1:p.His176Arg
  • NP_001393424.1:p.His92Arg
  • LRG_543t1:c.839A>G
  • LRG_543:g.12874A>G
  • LRG_543p1:p.His280Arg
  • NC_000012.11:g.52309075A>G
  • NM_000020.2:c.839A>G
Protein change:
H176R
Molecular consequence:
  • NM_000020.3:c.839A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001077401.2:c.839A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406487.1:c.839A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406488.1:c.839A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406489.1:c.839A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406490.1:c.527A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406491.1:c.527A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406492.1:c.527A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406493.1:c.527A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406494.1:c.527A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406495.1:c.275A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002677924Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Feb 15, 2022) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Update on molecular diagnosis of hereditary hemorrhagic telangiectasia.

Richards-Yutz J, Grant K, Chao EC, Walther SE, Ganguly A.

Hum Genet. 2010 Jul;128(1):61-77. doi: 10.1007/s00439-010-0825-4. Epub 2010 Apr 23.

PubMed [citation]
PMID:
20414677

Brain arteriovenous malformations associated with hereditary hemorrhagic telangiectasia: gene-phenotype correlations.

Nishida T, Faughnan ME, Krings T, Chakinala M, Gossage JR, Young WL, Kim H, Pourmohamad T, Henderson KJ, Schrum SD, James M, Quinnine N, Bharatha A, Terbrugge KG, White RI Jr.

Am J Med Genet A. 2012 Nov;158A(11):2829-34. doi: 10.1002/ajmg.a.35622. Epub 2012 Sep 18.

PubMed [citation]
PMID:
22991266
PMCID:
PMC3610331
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002677924.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

The p.H280R variant (also known as c.839A>G), located in coding exon 6 of the ACVRL1 gene, results from an A to G substitution at nucleotide position 839. The histidine at codon 280 is replaced by arginine, an amino acid with highly similar properties. This alteration has been reported in individuals with hereditary hemorrhagic telangiectasia (HHT) (Richards-Yutz J et al. Hum Genet, 2010 Jul;128:61-77; Nishida T et al. Am J Med Genet A, 2012 Nov;158A:2829-34; Komiyama M et al. J Hum Genet, 2014 Jan;59:37-41; Ambry Internal Data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: Aug 25, 2024