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NM_001077401.2(ACVRL1):c.1232G>A (p.Arg411Gln)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
10 (Most recent: Jul 4, 2021)
Last evaluated:
Oct 6, 2020
Accession:
VCV000008243.13
Variation ID:
8243
Description:
single nucleotide variant
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NM_001077401.2(ACVRL1):c.1232G>A (p.Arg411Gln)

Allele ID
23282
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
12q13.13
Genomic location
12: 51916219 (GRCh38) GRCh38 UCSC
12: 52310003 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000012.11:g.52310003G>A
NC_000012.12:g.51916219G>A
NM_000020.2:c.1232G>A NP_000011.2:p.Arg411Gln missense
... more HGVS
Protein change
R411Q
Other names
-
Canonical SPDI
NC_000012.12:51916218:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00001
Exome Aggregation Consortium (ExAC) 0.00001
Links
ClinGen: CA119395
UniProtKB: P37023#VAR_006213
OMIM: 601284.0001
dbSNP: rs121909284
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic/Likely pathogenic 7 criteria provided, multiple submitters, no conflicts Oct 6, 2020 RCV000008726.11
Pathogenic 2 criteria provided, multiple submitters, no conflicts Mar 1, 2020 RCV000522363.3
Pathogenic 1 no assertion criteria provided Apr 1, 2004 RCV000008727.2
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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

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Sep 08, 2017)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000617301.2
Submitted: (Jan 29, 2019)
Evidence details
Comment:
The R411Q pathogenic variant in the ACVRL1 gene has been reported in many times in association with HHT (Johnson et al., 1996; Berg et al., … (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: SCV001439399.1
Submitted: (May 21, 2020)
Evidence details
Publications
PubMed (1)
Comment:
PS3+PM2+PP4+PP5
Pathogenic
(Mar 11, 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: SCV000602399.2
Submitted: (Dec 11, 2020)
Evidence details
Comment:
The ACVRL1 c.1232G>A; p.Arg411Gln variant (rs121909284) has been reported in ClinVar (Variation ID: 8243), and described in the literature in multiple families with hereditary hemorrhagic … (more)
Pathogenic
(Oct 06, 2020)
criteria provided, single submitter
Method: clinical testing
Telangiectasia, hereditary hemorrhagic, type 2
Allele origin: germline
Invitae
Accession: SCV000552399.6
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (7)
Comment:
This sequence change replaces arginine with glutamine at codon 411 of the ACVRL1 protein (p.Arg411Gln). The arginine residue is highly conserved and there is a … (more)
Pathogenic
(Mar 01, 2020)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
CeGaT Praxis fuer Humangenetik Tuebingen
Accession: SCV001249011.5
Submitted: (Jul 04, 2021)
Evidence details
Pathogenic
(Oct 31, 2018)
criteria provided, single submitter
Method: clinical testing
Telangiectasia, hereditary hemorrhagic, type 2
Allele origin: unknown
Fulgent Genetics,Fulgent Genetics
Accession: SCV000893308.1
Submitted: (Nov 14, 2018)
Evidence details
Publications
PubMed (1)
DOI: 10.1038/gim.2015.30
Pathogenic
(Nov 20, 2018)
criteria provided, single submitter
Method: clinical testing
Telangiectasia, hereditary hemorrhagic, type 2
Allele origin: de novo
Laboratory of Medical Genetics, National & Kapodistrian University of Athens
Accession: SCV000928397.1
Submitted: (Mar 06, 2019)
Evidence details
Comment:
PM1, PM5, PP2, PP3, PP4, PP5
Pathogenic
(Oct 06, 2014)
no assertion criteria provided
Method: clinical testing
Hereditary hemorrhagic telangiectasia type 2
Allele origin: germline
Blueprint Genetics
Accession: SCV000206819.1
Submitted: (Feb 02, 2015)
Evidence details
Pathogenic
(Apr 01, 2004)
no assertion criteria provided
Method: literature only
TELANGIECTASIA, HEREDITARY HEMORRHAGIC, TYPE 2
Allele origin: germline
OMIM
Accession: SCV000028935.2
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (3)
Pathogenic
(Apr 01, 2004)
no assertion criteria provided
Method: literature only
PULMONARY ARTERIAL HYPERTENSION, HEREDITARY HEMORRHAGIC TELANGIECTASIA-RELATED
Allele origin: germline
OMIM
Accession: SCV000028936.2
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (3)

Functional evidence

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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

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Title Author Journal Year Link
Mutational and phenotypic characterization of hereditary hemorrhagic telangiectasia. Shovlin CL Blood 2020 PMID: 32573726
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
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Richards S Genetics in medicine : official journal of the American College of Medical Genetics 2015 PMID: 25741868
HHT diagnosis by Mid-infrared spectroscopy and artificial neural network analysis. Lux A Orphanet journal of rare diseases 2013 PMID: 23805858
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
Update on molecular diagnosis of hereditary hemorrhagic telangiectasia. Richards-Yutz J Human genetics 2010 PMID: 20414677
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
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 rs121909284...

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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 Jul 10, 2021