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NM_000020.2(ACVRL1):c.1135G>A (p.Glu379Lys)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
4 (Most recent: Jan 7, 2021)
Last evaluated:
Jul 13, 2020
Accession:
VCV000429940.4
Variation ID:
429940
Description:
single nucleotide variant
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NM_000020.2(ACVRL1):c.1135G>A (p.Glu379Lys)

Allele ID
421939
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
12q13.13
Genomic location
12: 51916122 (GRCh38) GRCh38 UCSC
12: 52309906 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000012.11:g.52309906G>A
NC_000012.12:g.51916122G>A
NM_000020.2:c.1135G>A NP_000011.2:p.Glu379Lys missense
... more HGVS
Protein change
E379K
Other names
-
Canonical SPDI
NC_000012.12:51916121:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00001
Links
ClinGen: CA384902497
dbSNP: rs1131691686
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 2 criteria provided, multiple submitters, no conflicts Jul 11, 2017 RCV000494459.1
Pathogenic 2 criteria provided, multiple submitters, no conflicts Jul 13, 2020 RCV000554533.4
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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
557 568

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Apr 20, 2016)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000582632.3
Submitted: (Nov 28, 2017)
Evidence details
Comment:
The E379K variant has been reported in multiple unrelated individuals from various ethnic backgrounds who have been diagnosed with HHT (Lesca et al., 2004; Brusgaard … (more)
Pathogenic
(Jul 11, 2017)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories
Accession: SCV000883354.1
Submitted: (Oct 10, 2018)
Evidence details
Comment:
The ACVRL1 c.1135G>A; p.Glu379Lys variant has been reported in several unrelated individuals diagnosed with hereditary hemorrhagic telangiectasia (Brakensiek 2008, Fontalba 2008, Kuehl 2005, Lenato 2006, … (more)
Pathogenic
(Jul 18, 2018)
criteria provided, single submitter
Method: clinical testing
Telangiectasia, hereditary hemorrhagic, type 2
Allele origin: germline
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001428881.1
Submitted: (Apr 20, 2020)
Evidence details
Pathogenic
(Jul 13, 2020)
criteria provided, single submitter
Method: clinical testing
Telangiectasia, hereditary hemorrhagic, type 2
Allele origin: germline
Invitae
Accession: SCV000639388.3
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (7)
Comment:
This sequence change replaces glutamic acid with lysine at codon 379 of the ACVRL1 protein (p.Glu379Lys). The glutamic acid residue is highly conserved and there … (more)

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
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
Long non-coding RNA expression profiles in hereditary haemorrhagic telangiectasia. Tørring PM PloS one 2014 PMID: 24603890
Brain arteriovenous malformations associated with hereditary hemorrhagic telangiectasia: gene-phenotype correlations. Nishida T American journal of medical genetics. Part A 2012 PMID: 22991266
Detection of a significant association between mutations in the ACVRL1 gene and hepatic involvement in German patients with hereditary haemorrhagic telangiectasia. Brakensiek K Clinical genetics 2008 PMID: 18498373
DHPLC-based mutation analysis of ENG and ALK-1 genes in HHT Italian population. Lenato GM Human mutation 2006 PMID: 16429404
Hepatic manifestation is associated with ALK1 in hereditary hemorrhagic telangiectasia: identification of five novel ALK1 and one novel ENG mutations. Kuehl HK Human mutation 2005 PMID: 15712270
Molecular screening of ALK1/ACVRL1 and ENG genes in hereditary hemorrhagic telangiectasia in France. Lesca G Human mutation 2004 PMID: 15024723

Text-mined citations for rs1131691686...

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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 May 10, 2021