NM_000020.3(ACVRL1):c.229T>C (p.Cys77Arg) AND Cardiovascular phenotype

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 26, 2016
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:: RCV002428464.1

Allele description

NM_000020.3(ACVRL1):c.229T>C (p.Cys77Arg)

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_000020.3(ACVRL1):c.229T>C (p.Cys77Arg)

HGVS:

NC_000012.12:g.51913266T>C
NG_009549.1:g.10849T>C
NM_000020.3:c.229T>CMANE SELECT
NM_001077401.2:c.229T>C
NM_001406487.1:c.229T>C
NM_001406488.1:c.229T>C
NM_001406489.1:c.229T>C
NM_001406490.1:c.229T>C
NM_001406491.1:c.229T>C
NM_001406492.1:c.229T>C
NM_001406493.1:c.229T>C
NM_001406494.1:c.229T>C
NP_000011.2:p.Cys77Arg
NP_000011.2:p.Cys77Arg
NP_001070869.1:p.Cys77Arg
NP_001393416.1:p.Cys77Arg
NP_001393417.1:p.Cys77Arg
NP_001393418.1:p.Cys77Arg
NP_001393419.1:p.Cys77Arg
NP_001393420.1:p.Cys77Arg
NP_001393421.1:p.Cys77Arg
NP_001393422.1:p.Cys77Arg
NP_001393423.1:p.Cys77Arg
LRG_543t1:c.229T>C
LRG_543:g.10849T>C
LRG_543p1:p.Cys77Arg
NC_000012.11:g.52307050T>C
NM_000020.2:c.229T>C

Protein change:

C77R

Molecular consequence:

NM_000020.3:c.229T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001077401.2:c.229T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406487.1:c.229T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406488.1:c.229T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406489.1:c.229T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406490.1:c.229T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406491.1:c.229T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406492.1:c.229T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406493.1:c.229T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406494.1:c.229T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002731726	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Likely pathogenic (Sep 26, 2016)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10694922, 17786384, 26176610 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002731726

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Likely pathogenic
(Sep 26, 2016)

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	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Novel missense and frameshift mutations in the activin receptor-like kinase-1 gene in hereditary hemorrhagic telangiectasia. Mutations in brief no. 164. Online.

Klaus DJ, Gallione CJ, Anthony K, Yeh EY, Yu J, Lux A, Johnson DW, Marchuk DA.

Hum Mutat. 1998;12(2):137.

PubMed [citation]

PMID:: 10694922

Analysis of ENG and ACVRL1 genes in 137 HHT Italian families identifies 76 different mutations (24 novel). Comparison with other European studies.

Olivieri C, Pagella F, Semino L, Lanzarini L, Valacca C, Pilotto A, Corno S, Scappaticci S, Manfredi G, Buscarini E, Danesino C.

J Hum Genet. 2007;52(10):820-829. doi: 10.1007/s10038-007-0187-5. Epub 2007 Sep 5.

PubMed [citation]

PMID:: 17786384

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002731726.1

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

Description

The p.C77R variant (also known as c.229T>C), located in coding exon 2 of the ACVRL1 gene, results from a T to C substitution at nucleotide position 229. The cysteine at codon 77 is replaced by arginine, an amino acid with highly dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6500 samples (13000 alleles) with coverage at this position. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Alterations at the same amino acid position, C77F (Alaa El Din F et al. PLoS ONE, 2015 Jul;10:e0132111), C77W (Klaus DJ et al. Hum. Mutat., 1998;12:137) and C77Y (Olivieri C et al. J. Hum. Genet., 2007 Sep;52:820-9), were reported in individuals with hereditary hemorrhagic telangiectasia. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: Nov 29, 2022

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