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NM_000020.3(ACVRL1):c.1468C>T (p.Gln490Ter) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 16, 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:
RCV002395186.2

Allele description [Variation Report for NM_000020.3(ACVRL1):c.1468C>T (p.Gln490Ter)]

NM_000020.3(ACVRL1):c.1468C>T (p.Gln490Ter)

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.1468C>T (p.Gln490Ter)
Other names:
p.Gln490*; NM_000020.3(ACVRL1):c.1468C>T; p.Gln490Ter
HGVS:
  • NC_000012.12:g.51920849C>T
  • NG_009549.1:g.18432C>T
  • NM_000020.3:c.1468C>TMANE SELECT
  • NM_001077401.2:c.1468C>T
  • NP_000011.2:p.Gln490Ter
  • NP_000011.2:p.Gln490Ter
  • NP_000011.2:p.Q490*
  • NP_001070869.1:p.Gln490Ter
  • LRG_543t1:c.1468C>T
  • LRG_543t1:c.1468C>T
  • LRG_543:g.18432C>T
  • LRG_543p1:p.Gln490Ter
  • LRG_543p1:p.Q490*
  • NC_000012.11:g.52314633C>T
  • NM_000020.2:c.1468C>T
Protein change:
Q490*
Links:
dbSNP: rs1085307429
NCBI 1000 Genomes Browser:
rs1085307429
Molecular consequence:
  • NM_000020.3:c.1468C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001077401.2:c.1468C>T - 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
SCV002697491Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Dec 16, 2021) 		germlineclinical testing

PubMed (6)
[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

Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia.

Trembath RC, Thomson JR, Machado RD, Morgan NV, Atkinson C, Winship I, Simonneau G, Galie N, Loyd JE, Humbert M, Nichols WC, Morrell NW, Berg J, Manes A, McGaughran J, Pauciulo M, Wheeler L.

N Engl J Med. 2001 Aug 2;345(5):325-34.

PubMed [citation]
PMID:
11484689

DHPLC-based mutation analysis of ENG and ALK-1 genes in HHT Italian population.

Lenato GM, Lastella P, Di Giacomo MC, Resta N, Suppressa P, Pasculli G, Sabbà C, Guanti G.

Hum Mutat. 2006 Feb;27(2):213-4.

PubMed [citation]
PMID:
16429404
See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV002697491.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

The p.Q490* pathogenic mutation (also known as c.1468C>T), located in coding exon 9 of the ACVRL1 gene, results from a C to T substitution at nucleotide position 1468. This changes the amino acid from a glutamine to a stop codon within coding exon 9. This alteration occurs at the 3' terminus of theACVRL1 gene, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 2.8% of the protein. However, premature stop codons are typically deleterious in nature and a significant portion of the protein is affected (Ambry internal data). This alteration has been reported in individuals with a clinical diagnosis of hereditary hemorrhagic telangiectasia (HHT), as well as in individuals with concerns for HHT (El-Harith et al. Eur J Med Genet 2006 Oct;49:323-30; Lenato GM et al. Hum Mutat, 2006 Feb;27:213-4; Olivieri C et al. Genet Med, 2006 Mar;8:183-90; Tørring PM et al. Clin Genet, 2014 Aug;86:123-33). Additionally, this alteration segregated with disease in one family (Trembath RC et al. N. Engl. J. Med., 2001 Aug;345:325-34). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: May 1, 2024