Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation

ClinVar Genomic variation as it relates to human health

Advanced search

NM_000020.2(ACVRL1):c.1231C>T (p.Arg411Trp)

Help
Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
7 (Most recent: May 26, 2021)
Last evaluated:
Oct 29, 2020
Accession:
VCV000008251.8
Variation ID:
8251
Description:
single nucleotide variant
Help

NM_000020.2(ACVRL1):c.1231C>T (p.Arg411Trp)

Allele ID
23290
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
12q13.13
Genomic location
12: 51916218 (GRCh38) GRCh38 UCSC
12: 52310002 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000012.11:g.52310002C>T
NC_000012.12:g.51916218C>T
NM_000020.2:c.1231C>T NP_000011.2:p.Arg411Trp missense
... more HGVS
Protein change
R411W
Other names
p.R411W:CGG>TGG
Canonical SPDI
NC_000012.12:51916217:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA119402
UniProtKB: P37023#VAR_026809
OMIM: 601284.0009
dbSNP: rs121909287
Varsome
Help

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic/Likely pathogenic 4 criteria provided, multiple submitters, no conflicts Oct 29, 2020 RCV000008737.10
Pathogenic 2 criteria provided, multiple submitters, no conflicts Jun 4, 2020 RCV000199381.3
Pathogenic 1 no assertion criteria provided Jun 1, 2008 RCV000008738.2
Help
Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
ACVRL1 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
568 579

Submitted interpretations and evidence

Help
Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Nov 15, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000249635.11
Submitted: (Jan 29, 2019)
Evidence details
Comment:
The R411W pathogenic variant in the ACVRL1 gene has been reported in association with HHT and PAH (Trembath et al., 2001; Abdalla et al., 2003; … (more)
Likely pathogenic
(Jan 01, 2018)
criteria provided, single submitter
Method: research
Telangiectasia, hereditary hemorrhagic, type 2
Allele origin: unknown
NIHR Bioresource Rare Diseases, University of Cambridge
Accession: SCV001439398.1
Submitted: (May 21, 2020)
Evidence details
Publications
PubMed (1)
Comment:
PS3+PM2+PP4+PP5
Pathogenic
(Apr 04, 2020)
criteria provided, single submitter
Method: clinical testing
Telangiectasia, hereditary hemorrhagic, type 2
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories
Accession: SCV001156568.2
Submitted: (Dec 11, 2020)
Evidence details
Comment:
The ACVRL1 c.1231C>T; p.Arg411Trp variant (rs121909287) is reported in multiple individuals with hereditary hemorrhagic telangiectasia (HHT) and/or pulmonary arterial hypertension (PAH), and has been shown … (more)
Pathogenic
(Oct 29, 2020)
criteria provided, single submitter
Method: clinical testing
Telangiectasia, hereditary hemorrhagic, type 2
Allele origin: germline
Invitae
Accession: SCV000552419.6
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (9)
Comment:
This sequence change replaces arginine with tryptophan at codon 411 of the ACVRL1 protein (p.Arg411Trp). The arginine residue is highly conserved and there is a … (more)
Pathogenic
(Jun 04, 2020)
criteria provided, single submitter
Method: clinical testing
Not provided
Allele origin: germline
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001715008.1
Submitted: (May 26, 2021)
Evidence details
Publications
PubMed (7)
Comment:
PS3, PS4_Moderate, PM1, PM2, PM5, PP1, PP3
Pathogenic
(Jun 01, 2008)
no assertion criteria provided
Method: literature only
TELANGIECTASIA, HEREDITARY HEMORRHAGIC, TYPE 2
Allele origin: germline
OMIM
Accession: SCV000028946.2
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (3)
Pathogenic
(Jun 01, 2008)
no assertion criteria provided
Method: literature only
PULMONARY ARTERIAL HYPERTENSION, HEREDITARY HEMORRHAGIC TELANGIECTASIA-RELATED
Allele origin: germline
OMIM
Accession: SCV000028947.2
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (3)

Functional evidence

Help
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

Help
Title Author Journal Year Link
Mutational and phenotypic characterization of hereditary hemorrhagic telangiectasia. Shovlin CL Blood 2020 PMID: 32573726
Germline <i>BMP9</i> mutation causes idiopathic pulmonary arterial hypertension. Wang XJ The European respiratory journal 2019 PMID: 30578397
Exome Sequencing in Children With Pulmonary Arterial Hypertension Demonstrates Differences Compared With Adults. Zhu N Circulation. Genomic and precision medicine 2018 PMID: 29631995
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
Identification of multiple ACVRL1 mutations in patients with pulmonary arterial hypertension by targeted exome capture. Piao C Clinical science (London, England : 1979) 2016 PMID: 27316748
Functional and splicing defect analysis of 23 ACVRL1 mutations in a cohort of patients affected by Hereditary Hemorrhagic Telangiectasia. Alaa El Din F PloS one 2015 PMID: 26176610
Retention in the endoplasmic reticulum is the underlying mechanism of some hereditary haemorrhagic telangiectasia type 2 ALK1 missense mutations. Hume AN Molecular and cellular biochemistry 2013 PMID: 23124896
Functional analysis of the BMP9 response of ALK1 mutants from HHT2 patients: a diagnostic tool for novel ACVRL1 mutations. Ricard N Blood 2010 PMID: 20501893
Hereditary hemorrhagic telangiectasia: evidence for regional founder effects of ACVRL1 mutations in French and Italian patients. Lesca G European journal of human genetics : EJHG 2008 PMID: 18285823
High frequency of ENG and ALK1/ACVRL1 mutations in German HHT patients. Schulte C Human mutation 2005 PMID: 15880681
Molecular screening of ALK1/ACVRL1 and ENG genes in hereditary hemorrhagic telangiectasia in France. Lesca G Human mutation 2004 PMID: 15024723
Molecular and functional analysis identifies ALK-1 as the predominant cause of pulmonary hypertension related to hereditary haemorrhagic telangiectasia. Harrison RE Journal of medical genetics 2003 PMID: 14684682
Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia. Trembath RC The New England journal of medicine 2001 PMID: 11484689
Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2. Johnson DW Nature genetics 1996 PMID: 8640225

Text-mined citations for rs121909287...

Help
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 Jun 14, 2021