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NM_000020.3(ACVRL1):c.663G>A (p.Trp221Ter) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 6, 2023
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:
RCV003170168.2

Allele description [Variation Report for NM_000020.3(ACVRL1):c.663G>A (p.Trp221Ter)]

NM_000020.3(ACVRL1):c.663G>A (p.Trp221Ter)

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.663G>A (p.Trp221Ter)
HGVS:
  • NC_000012.12:g.51914476G>A
  • NG_009549.1:g.12059G>A
  • NM_000020.2:c.663G>A
  • NM_000020.3:c.663G>AMANE SELECT
  • NM_001077401.2:c.663G>A
  • NP_000011.2:p.Trp221Ter
  • NP_001070869.1:p.Trp221Ter
  • LRG_543t1:c.663G>A
  • LRG_543:g.12059G>A
  • NC_000012.11:g.52308260G>A
Protein change:
W221*
Links:
dbSNP: rs2139070482
NCBI 1000 Genomes Browser:
rs2139070482
Molecular consequence:
  • NM_000020.3:c.663G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001077401.2:c.663G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003899897Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jan 6, 2023) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Mutation study of Spanish patients with hereditary hemorrhagic telangiectasia.

Fontalba A, Fernandez-L A, García-Alegria E, Albiñana V, Garrido-Martin EM, Blanco FJ, Zarrabeitia R, Perez-Molino A, Bernabeu-Herrero ME, Ojeda ML, Fernandez-Luna JL, Bernabeu C, Botella LM.

BMC Med Genet. 2008 Aug 1;9:75. doi: 10.1186/1471-2350-9-75.

PubMed [citation]
PMID:
18673552
PMCID:
PMC2518546

Molecular diagnosis in hereditary hemorrhagic telangiectasia: findings in a series tested simultaneously by sequencing and deletion/duplication analysis.

McDonald J, Damjanovich K, Millson A, Wooderchak W, Chibuk JM, Stevenson DA, Gedge F, Bayrak-Toydemir P.

Clin Genet. 2011 Apr;79(4):335-44. doi: 10.1111/j.1399-0004.2010.01596.x. Epub 2010 Dec 16.

PubMed [citation]
PMID:
21158752
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV003899897.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

The p.W221* pathogenic mutation (also known as c.663G>A), located in coding exon 5 of the ACVRL1 gene, results from a G to A substitution at nucleotide position 663. This changes the amino acid from a tryptophan to a stop codon within coding exon 5. This alteration has been reported in hereditary hemorrhagic telangiectasia (HHT) cohorts and a pulmonary arterial hypertension cohort (Fontalba A et al. BMC Med Genet, 2008 Aug;9:75; McDonald J et al. Clin Genet, 2011 Apr;79:335-44; Song J et al. Clin Sci (Lond), 2016 Nov;130:2043-2052). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.

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

Last Updated: Sep 29, 2024