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NM_003239.5(TGFB3):c.463C>T (p.Arg155Trp) AND Familial thoracic aortic aneurysm and aortic dissection

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 14, 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:
RCV002334211.9

Allele description [Variation Report for NM_003239.5(TGFB3):c.463C>T (p.Arg155Trp)]

NM_003239.5(TGFB3):c.463C>T (p.Arg155Trp)

Gene:
TGFB3:transforming growth factor beta 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q24.3
Genomic location:
Preferred name:
NM_003239.5(TGFB3):c.463C>T (p.Arg155Trp)
HGVS:
  • NC_000014.9:g.75971608G>A
  • NG_011715.1:g.15142C>T
  • NM_001329938.2:c.463C>T
  • NM_001329939.2:c.463C>T
  • NM_003239.5:c.463C>TMANE SELECT
  • NP_001316867.1:p.Arg155Trp
  • NP_001316868.1:p.Arg155Trp
  • NP_003230.1:p.Arg155Trp
  • LRG_399t1:c.463C>T
  • LRG_399:g.15142C>T
  • NC_000014.8:g.76437951G>A
  • NM_003239.2:c.463C>T
  • NM_003239.3:c.463C>T
Protein change:
R155W
Links:
dbSNP: rs868258653
NCBI 1000 Genomes Browser:
rs868258653
Molecular consequence:
  • NM_001329938.2:c.463C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001329939.2:c.463C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003239.5:c.463C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002635275Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Oct 14, 2021) 		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

Prodomain-growth factor swapping in the structure of pro-TGF-β1.

Zhao B, Xu S, Dong X, Lu C, Springer TA.

J Biol Chem. 2018 Feb 2;293(5):1579-1589. doi: 10.1074/jbc.M117.809657. Epub 2017 Nov 5.

PubMed [citation]
PMID:
29109152
PMCID:
PMC5798290

Phenotypic spectrum of TGFB3 disease-causing variants in a Dutch-French cohort and first report of a homozygous patient.

Marsili L, Overwater E, Hanna N, Baujat G, Baars MJH, Boileau C, Bonneau D, Brehin AC, Capri Y, Cheung HY, Dulfer E, Gerard M, Gouya L, Hilhorst-Hofstee Y, Houweling AC, Isidor B, Le Gloan L, Menke LA, Odent S, Morice-Picard F, Vanlerberghe C, Voorhoeve E, et al.

Clin Genet. 2020 May;97(5):723-730. doi: 10.1111/cge.13700. Epub 2020 Jan 16.

PubMed [citation]
PMID:
31898322
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002635275.2

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

Description

The p.R155W variant (also known as c.463C>T), located in coding exon 2 of the TGFB3 gene, results from a C to T substitution at nucleotide position 463. The arginine at codon 155 is replaced by tryptophan, an amino acid with dissimilar properties. This variant has been reported in affected individuals with features of Loeys-Dietz syndrome, including aortic dissection, tortuosity of the vertebral arteries, bifid uvula, and/ or other connective tissue disease findings (Verstraeten A et al. Circulation, 2020 09;142:1021-1024; Marsili L et al. Clin Genet, 2020 05;97:723-730). Based on internal structural analysis, p.R155W decreases the structure stability (Ambry internal data; Zhao B et al. J Biol Chem, 2018 02;293:1579-1589). This variant is considered to be rare based on population 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
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 25, 2024