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NM_000020.3(ACVRL1):c.1436G>A (p.Arg479Gln) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 18, 2021
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:
RCV002395185.2

Allele description [Variation Report for NM_000020.3(ACVRL1):c.1436G>A (p.Arg479Gln)]

NM_000020.3(ACVRL1):c.1436G>A (p.Arg479Gln)

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.1436G>A (p.Arg479Gln)
HGVS:
  • NC_000012.12:g.51920817G>A
  • NG_009549.1:g.18400G>A
  • NM_000020.3:c.1436G>AMANE SELECT
  • NM_001077401.2:c.1436G>A
  • NP_000011.2:p.Arg479Gln
  • NP_000011.2:p.Arg479Gln
  • NP_001070869.1:p.Arg479Gln
  • LRG_543t1:c.1436G>A
  • LRG_543:g.18400G>A
  • LRG_543p1:p.Arg479Gln
  • NC_000012.11:g.52314601G>A
  • NM_000020.2:c.1436G>A
Protein change:
R479Q
Links:
dbSNP: rs1085307426
NCBI 1000 Genomes Browser:
rs1085307426
Molecular consequence:
  • NM_000020.3:c.1436G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001077401.2:c.1436G>A - 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
SCV002702858Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Aug 18, 2021) 		germlineclinical testing

PubMed (6)
[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

Genotype-phenotype correlation in hereditary hemorrhagic telangiectasia: mutations and manifestations.

Bayrak-Toydemir P, McDonald J, Markewitz B, Lewin S, Miller F, Chou LS, Gedge F, Tang W, Coon H, Mao R.

Am J Med Genet A. 2006 Mar 1;140(5):463-70.

PubMed [citation]
PMID:
16470787

Distribution of ENG and ACVRL1 (ALK1) mutations in French HHT patients.

Lesca G, Burnichon N, Raux G, Tosi M, Pinson S, Marion MJ, Babin E, Gilbert-Dussardier B, Rivière S, Goizet C, Faivre L, Plauchu H, Frébourg T, Calender A, Giraud S; French Rendu-Osler Network..

Hum Mutat. 2006 Jun;27(6):598.

PubMed [citation]
PMID:
16705692
See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV002702858.2

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

Description

The p.R479Q pathogenic mutation (also known as c.1436G>A), located in coding exon 9 of the ACVRL1 gene, results from a G to A substitution at nucleotide position 1436. The arginine at codon 479 is replaced by glutamine, an amino acid with highly similar properties. This mutation has been reported in multiple individuals meeting clinical diagnostic criteria for hereditary hemorrhagic telangiectasia (Bayrak-Toydemir P et al. Am. J. Med. Genet. A, 2006 Mar;140:463-70; Lesca G et al. Hum. Mutat., 2006 Jun;27:598; Giordano P et al. J. Pediatr., 2013 Jul;163:179-86.e1-3) and it has been shown to co-segregate with disease (Bayrak-Toydemir P et al. Exp. Mol. Pathol., 2008 Aug;85:45-9). In addition, an in vitro functional study demonstrated that although this mutation does not disrupt ligand binding, it does interfere with ligand signaling (Ricard N et al. Blood, 2010 Sep;116:1604-12). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Sep 29, 2024