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NM_000020.3(ACVRL1):c.1120C>T (p.Arg374Trp) AND Pulmonary arterial hypertension related to hereditary hemorrhagic telangiectasia

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Jun 1, 2008
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000008734.5

Allele description [Variation Report for NM_000020.3(ACVRL1):c.1120C>T (p.Arg374Trp)]

NM_000020.3(ACVRL1):c.1120C>T (p.Arg374Trp)

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.1120C>T (p.Arg374Trp)
HGVS:
  • NC_000012.12:g.51916107C>T
  • NG_009549.1:g.13690C>T
  • NM_000020.3:c.1120C>TMANE SELECT
  • NM_001077401.2:c.1120C>T
  • NP_000011.2:p.Arg374Trp
  • NP_000011.2:p.Arg374Trp
  • NP_001070869.1:p.Arg374Trp
  • LRG_543t1:c.1120C>T
  • LRG_543:g.13690C>T
  • LRG_543p1:p.Arg374Trp
  • NC_000012.11:g.52309891C>T
  • NM_000020.2:c.1120C>T
  • NM_001077401.2:c.1120C>T
  • NP_000011.2:p.R374W
  • P37023:p.Arg374Trp
Protein change:
R374W; ARG374TRP
Links:
UniProtKB: P37023#VAR_006211; OMIM: 601284.0007; dbSNP: rs28936401
NCBI 1000 Genomes Browser:
rs28936401
Molecular consequence:
  • NM_000020.3:c.1120C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001077401.2:c.1120C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Pulmonary arterial hypertension related to hereditary hemorrhagic telangiectasia
Synonyms:
PULMONARY ARTERIAL HYPERTENSION, HEREDITARY HEMORRHAGIC TELANGIECTASIA-RELATED
Identifiers:
MedGen: C1832529

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000028943OMIM
no assertion criteria provided
Pathogenic
(Jun 1, 2008) 		germlineliterature only

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

SCV000576330Rare Disease Genomics Group, St George's University of London
no assertion criteria provided
Pathogenicgermlineliterature only

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedliterature only
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Mutations in the ALK-1 gene and the phenotype of hereditary hemorrhagic telangiectasia in two large Danish families.

Kjeldsen AD, Brusgaard K, Poulsen L, Kruse T, Rasmussen K, Green A, Vase P.

Am J Med Genet. 2001 Feb 1;98(4):298-302.

PubMed [citation]
PMID:
11170071

Hereditary hemorrhagic telangiectasia: evidence for regional founder effects of ACVRL1 mutations in French and Italian patients.

Lesca G, Genin E, Blachier C, Olivieri C, Coulet F, Brunet G, Dupuis-Girod S, Buscarini E, Soubrier F, Calender A, Danesino C, Giraud S, Plauchu H; French-Italian HHT Network..

Eur J Hum Genet. 2008 Jun;16(6):742-9. doi: 10.1038/ejhg.2008.3. Epub 2008 Feb 20.

PubMed [citation]
PMID:
18285823
See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000028943.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (3)

Description

In affected members of a family with hereditary hemorrhagic telangiectasia (HHT2; 600376), Kjeldsen et al. (2001) identified an 1120C-T transition in exon 8 of the ALK1 gene, resulting in an arg374-to-trp (R374W) substitution. No affected patients had pulmonary arteriovenous malformations, and only 1 patient had a history of severe gastrointestinal bleeding.

In a population-based study of primarily French HHT2 patients, Lesca et al. (2008) showed that the R374W mutation associated with a shared ancestral haplotype in a subset of patients, suggesting a founder effect with the mutation arising approximately 300 years ago. In other patients, the mutation was related to different independent mutation events.

In a 41-year-old woman with hereditary hemorrhagic telangiectasis-related pulmonary arterial hypertension (see 600376), Harrison et al. (2003) identified the R374W mutation. The patient had an atrial septal defect repaired before the onset of significantly raised pulmonary artery pressure, and also had a sib with primary pulmonary hypertension (see 178600).

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

From Rare Disease Genomics Group, St George's University of London, SCV000576330.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (3)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 8, 2024