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NM_001613.4(ACTA2):c.352C>T (p.Arg118Trp) AND Familial thoracic aortic aneurysm and aortic dissection

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Feb 4, 2022
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:
RCV002456554.1

Allele description

NM_001613.4(ACTA2):c.352C>T (p.Arg118Trp)

Gene:
ACTA2:actin alpha 2, smooth muscle [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10q23.31
Genomic location:
Preferred name:
NM_001613.4(ACTA2):c.352C>T (p.Arg118Trp)
HGVS:
  • NC_000010.11:g.88943814G>A
  • NG_011541.1:g.52577C>T
  • NM_001141945.3:c.352C>T
  • NM_001320855.2:c.352C>T
  • NM_001406462.1:c.352C>T
  • NM_001406463.1:c.352C>T
  • NM_001406464.1:c.352C>T
  • NM_001406467.1:c.223C>T
  • NM_001406468.1:c.223C>T
  • NM_001406469.1:c.223C>T
  • NM_001406471.1:c.352C>T
  • NM_001613.4:c.352C>TMANE SELECT
  • NP_001135417.1:p.Arg118Trp
  • NP_001135417.1:p.Arg118Trp
  • NP_001135417.1:p.Arg118Trp
  • NP_001307784.1:p.Arg118Trp
  • NP_001307784.1:p.Arg118Trp
  • NP_001393391.1:p.Arg118Trp
  • NP_001393392.1:p.Arg118Trp
  • NP_001393393.1:p.Arg118Trp
  • NP_001393396.1:p.Arg75Trp
  • NP_001393397.1:p.Arg75Trp
  • NP_001393398.1:p.Arg75Trp
  • NP_001393400.1:p.Arg118Trp
  • NP_001604.1:p.Arg118Trp
  • NP_001604.1:p.Arg118Trp
  • LRG_781t1:c.352C>T
  • LRG_781t2:c.352C>T
  • LRG_781:g.52577C>T
  • LRG_781p1:p.Arg118Trp
  • LRG_781p2:p.Arg118Trp
  • NC_000010.10:g.90703571G>A
  • NM_001141945.1:c.352C>T
  • NM_001141945.2:c.352C>T
  • NM_001320855.1:c.352C>T
  • NM_001613.2:c.352C>T
  • NM_001613.2:c.352C>T
Protein change:
R118W
Links:
dbSNP: rs1845899655
NCBI 1000 Genomes Browser:
rs1845899655
Molecular consequence:
  • NM_001141945.3:c.352C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001320855.2:c.352C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406462.1:c.352C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406463.1:c.352C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406464.1:c.352C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406467.1:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406468.1:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406469.1:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001406471.1:c.352C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001613.4:c.352C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Familial thoracic aortic aneurysm and aortic dissection (TAAD)
Synonyms:
Thoracic aortic aneurysm and aortic dissection; Thoracic aortic aneurysms and dissections
Identifiers:
MONDO: MONDO:0019625; MedGen: C4707243; Orphanet: 91387; OMIM: PS607086

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002616144Ambry Genetics
criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)		Likely pathogenic
(Feb 4, 2022) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Structures of the Phactr1 RPEL domain and RPEL motif complexes with G-actin reveal the molecular basis for actin binding cooperativity.

Mouilleron S, Wiezlak M, O'Reilly N, Treisman R, McDonald NQ.

Structure. 2012 Nov 7;20(11):1960-70. doi: 10.1016/j.str.2012.08.031. Epub 2012 Oct 4.

PubMed [citation]
PMID:
23041370

Structural transitions of F-actin upon ATP hydrolysis at near-atomic resolution revealed by cryo-EM.

Merino F, Pospich S, Funk J, Wagner T, Küllmer F, Arndt HD, Bieling P, Raunser S.

Nat Struct Mol Biol. 2018 Jun;25(6):528-537. doi: 10.1038/s41594-018-0074-0. Epub 2018 Jun 4.

PubMed [citation]
PMID:
29867215

Details of each submission

From Ambry Genetics, SCV002616144.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)

Description

The p.R118W variant (also known as c.352C>T), located in coding exon 3 of the ACTA2 gene, results from a C to T substitution at nucleotide position 352. The arginine at codon 118 is replaced by tryptophan, an amino acid with dissimilar properties. An alternate amino acid substitution at this position, p.R118Q (c.353G>A), has been reported to segregate with thoracic aortic aneurysm and dissection in multiple families (Guo DC et al. Nat. Genet., 2007 Dec;39:1488-93; Guo DC et al. Am. J. Hum. Genet., 2009 May;84:617-27; Bee KJ et al. Circ Cardiovasc Genet, 2012 Dec;5:621-9). In addition, based on internal structural assessment, the p.R118W alteration disrupts the structure of actin (Merino F et al. Nat. Struct. Mol. Biol., 2018 06;25:528-537; Mouilleron S et al. Structure, 2012 Nov;20:1960-70). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Feb 28, 2024