NM_000020.2(ACVRL1):c.1135G>A (p.Glu379Lys) AND Telangiectasia, hereditary hemorrhagic, type 2

Clinical significance:Pathogenic (Last evaluated: Jul 13, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000554533.4

Allele description [Variation Report for NM_000020.2(ACVRL1):c.1135G>A (p.Glu379Lys)]

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

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_000020.2(ACVRL1):c.1135G>A (p.Glu379Lys)
HGVS:
  • NC_000012.12:g.51916122G>A
  • NG_009549.1:g.13705G>A
  • NM_000020.2:c.1135G>A
  • NM_001077401.2:c.1135G>A
  • NP_000011.2:p.Glu379Lys
  • NP_001070869.1:p.Glu379Lys
  • LRG_543t1:c.1135G>A
  • LRG_543:g.13705G>A
  • LRG_543p1:p.Glu379Lys
  • NC_000012.11:g.52309906G>A
Protein change:
E379K
Links:
dbSNP: rs1131691686
NCBI 1000 Genomes Browser:
rs1131691686
Molecular consequence:
  • NM_000020.2:c.1135G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001077401.2:c.1135G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Telangiectasia, hereditary hemorrhagic, type 2 (HHT2)
Synonyms:
Telangiectasia, hereditary hemorrhagic, type II; Osler Weber Rendu syndrome type 2
Identifiers:
MONDO: MONDO:0010880; MedGen: C1838163; Orphanet: 774; OMIM: 600376

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000639388Invitaecriteria provided, single submitter
Pathogenic
(Jul 13, 2020)
germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

SCV001428881Institute of Human Genetics, University of Leipzig Medical Centercriteria provided, single submitter
Pathogenic
(Jul 18, 2018)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Molecular screening of ALK1/ACVRL1 and ENG genes in hereditary hemorrhagic telangiectasia in France.

Lesca G, Plauchu H, Coulet F, Lefebvre S, Plessis G, Odent S, Rivière S, Leheup B, Goizet C, Carette MF, Cordier JF, Pinson S, Soubrier F, Calender A, Giraud S; French Rendu-Osler Network..

Hum Mutat. 2004 Apr;23(4):289-99.

PubMed [citation]
PMID:
15024723

Hepatic manifestation is associated with ALK1 in hereditary hemorrhagic telangiectasia: identification of five novel ALK1 and one novel ENG mutations.

Kuehl HK, Caselitz M, Hasenkamp S, Wagner S, El-Harith el-HA, Manns MP, Stuhrmann M.

Hum Mutat. 2005 Mar;25(3):320.

PubMed [citation]
PMID:
15712270
See all PubMed Citations (9)

Details of each submission

From Invitae, SCV000639388.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

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 is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in many unrelated individuals affected with hereditary hemorrhagic telangiectasia (PMID: 15024723, 15712270, 16429404, 18498373, 22991266, 24603890). Experimental studies have shown that this missense change causes mis-localization of the protein (PMID: 26176610). For these reasons, this variant has been classified as Pathogenic.

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

From Institute of Human Genetics, University of Leipzig Medical Center, SCV001428881.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

Last Updated: May 10, 2021

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