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NM_000020.3(ACVRL1):c.140G>C (p.Arg47Pro) AND Cardiovascular phenotype

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 10, 2016
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:
RCV002392977.2

Allele description [Variation Report for NM_000020.3(ACVRL1):c.140G>C (p.Arg47Pro)]

NM_000020.3(ACVRL1):c.140G>C (p.Arg47Pro)

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.140G>C (p.Arg47Pro)
HGVS:
  • NC_000012.12:g.51913177G>C
  • NG_009549.1:g.10760G>C
  • NM_000020.3:c.140G>CMANE SELECT
  • NM_001077401.2:c.140G>C
  • NP_000011.2:p.Arg47Pro
  • NP_000011.2:p.Arg47Pro
  • NP_001070869.1:p.Arg47Pro
  • LRG_543t1:c.140G>C
  • LRG_543:g.10760G>C
  • LRG_543p1:p.Arg47Pro
  • NC_000012.11:g.52306961G>C
  • NM_000020.2:c.140G>C
Protein change:
R47P
Links:
dbSNP: rs774389618
NCBI 1000 Genomes Browser:
rs774389618
Molecular consequence:
  • NM_000020.3:c.140G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001077401.2:c.140G>C - 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
SCV002701748Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Oct 10, 2016) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

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

Citations

PubMed

Mutation study of Spanish patients with hereditary hemorrhagic telangiectasia and expression analysis of Endoglin and ALK1.

Fernandez-L A, Sanz-Rodriguez F, Zarrabeitia R, Perez-Molino A, Morales C, Restrepo CM, Ramirez JR, Coto E, Lenato GM, Bernabeu C, Botella LM.

Hum Mutat. 2006 Mar;27(3):295.

PubMed [citation]
PMID:
16470589

Mutation analysis in hereditary haemorrhagic telangiectasia in Germany reveals 11 novel ENG and 12 novel ACVRL1/ALK1 mutations.

Wehner LE, Folz BJ, Argyriou L, Twelkemeyer S, Teske U, Geisthoff UW, Werner JA, Engel W, Nayernia K.

Clin Genet. 2006 Mar;69(3):239-45.

PubMed [citation]
PMID:
16542389
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002701748.2

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

Description

The p.R47P variant (also known as c.140G>C), located in coding exon 2 of the ACVRL1 gene, results from a G to C substitution at nucleotide position 140. The arginine at codon 47 is replaced by proline, an amino acid with dissimilar properties. This variant was described in a Spanish family in which the proband had a clinical diagnosis of hereditary hemorrhagic telangiectasia (HHT), including cerebral and hepatic arteriovenous malformations; the alteration was also detected in five other family members with epistaxis and telangiectasias (Fernandez-L A et al. Hum. Mutat., 2006 Mar;27:295). Kinetic and thermodynamic study indicates that this variant causes protein misfolding and aggregation which leads to defective binding to BMP9 in the ALK1 signaling pathway (Townson et al 2012, J. Biol. Chem., 287:27313-27325). This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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: Sep 29, 2024