NM_000020.3(ACVRL1):c.540_541insA (p.Asp181fs) AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 10, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002350270.2

Allele description [Variation Report for NM_000020.3(ACVRL1):c.540_541insA (p.Asp181fs)]

NM_000020.3(ACVRL1):c.540_541insA (p.Asp181fs)

Gene:

ACVRL1:activin A receptor like type 1 [Gene - OMIM - HGNC]

Variant type:

Insertion

Cytogenetic location:

12q13.13

Genomic location:

Preferred name:

NM_000020.3(ACVRL1):c.540_541insA (p.Asp181fs)

HGVS:

NC_000012.12:g.51913988_51913989insA
NG_009549.1:g.11571_11572insA
NM_000020.3:c.540_541insAMANE SELECT
NM_001077401.2:c.540_541insA
NP_000011.2:p.Asp181fs
NP_000011.2:p.Asp181fs
NP_001070869.1:p.Asp181fs
LRG_543t1:c.540_541insA
LRG_543:g.11571_11572insA
LRG_543p1:p.Asp181fs
NC_000012.11:g.52307772_52307773insA
NM_000020.2:c.540_541insA

Protein change:

D181fs

Links:

dbSNP: rs1555152774

NCBI 1000 Genomes Browser:

rs1555152774

Molecular consequence:

NM_000020.3:c.540_541insA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001077401.2:c.540_541insA - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

Recent activity

Clear Turn Off Turn On

Homo sapiens FERM domain containing 8 (FRMD8), transcript variant 1, mRNA
Homo sapiens FERM domain containing 8 (FRMD8), transcript variant 1, mRNA
gi|1519315772|ref|NM_031904.5|

Nucleotide
Homo sapiens Jrk helix-turn-helix protein (JRK), transcript variant 1, mRNA
Homo sapiens Jrk helix-turn-helix protein (JRK), transcript variant 1, mRNA
gi|1705442040|ref|NM_003724.4|

Nucleotide
glycoside hydrolase family 2 protein [Blautia pseudococcoides]
glycoside hydrolase family 2 protein [Blautia pseudococcoides]
gi|1957933713|gnl|PRJNA680355|I5Q86 5|gb|QQQ93614.1|

Protein
transcription factor, Fur family [synthetic bacterium JCVI-Syn3.0]
transcription factor, Fur family [synthetic bacterium JCVI-Syn3.0]
gi|1015828636|gb|AMW76581.1||gnl|PR 2950|JCVISYN3_0620

Protein
FS400464 normalized full-length tobacco cDNA library Nicotiana tabacum cDNA clon...
FS400464 normalized full-length tobacco cDNA library Nicotiana tabacum cDNA clone TBK01A01NGRL0077_4_C06 5', mRNA sequence
gi|254604633|gnl|dbEST|66633142|dbj 0464.1|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002650994	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (May 10, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16542389, 19508727, 21158752 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002650994

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(May 10, 2021)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutation analysis in hereditary haemorrhagic telangiectasia in Germany reveals 11 novel ENG and 12 novel ACVRL1/ALK1 mutations.

Wehner LE, Folz BJ, Argyriou L, Twelkemeyer S, Teske U, Geisthoff UW, Werner JA, Engel W, Nayernia K.

Clin Genet. 2006 Mar;69(3):239-45.

PubMed [citation]

PMID:: 16542389

Mutation analysis of "Endoglin" and "Activin receptor-like kinase" genes in German patients with hereditary hemorrhagic telangiectasia and the value of rapid genotyping using an allele-specific PCR-technique.

Sadick H, Hage J, Goessler U, Stern-Straeter J, Riedel F, Hoermann K, Bugert P.

BMC Med Genet. 2009 Jun 9;10:53. doi: 10.1186/1471-2350-10-53.

PubMed [citation]

PMID:: 19508727
PMCID:: PMC2701415

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002650994.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The c.540_541insA pathogenic mutation, located in coding exon 4 of the ACVRL1 gene, results from an insertion of one nucleotide at position 540, causing a translational frameshift with a predicted alternate stop codon (p.D181Rfs*44). This mutation was identified in multiple German individuals, including three individuals from one family with epistaxis and telangiectasias (Wehner LE et al. Clin. Genet., 2006 Mar;69:239-45; Sadick H et al. BMC Med. Genet., 2009 Jun;10:53). This mutation was also reported in one individual from an hereditary hemorrhagic telangiectasia (HHT) genetic testing cohort (McDonald J et al. Clin Genet, 2011 Apr;79:335-44). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

ClinVar

Relating variation to medicine