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NM_003239.5(TGFB3):c.787G>C (p.Asp263His) AND Rienhoff syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 7, 2015
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000185632.3

Allele description [Variation Report for NM_003239.5(TGFB3):c.787G>C (p.Asp263His)]

NM_003239.5(TGFB3):c.787G>C (p.Asp263His)

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.787G>C (p.Asp263His)
HGVS:
  • NC_000014.9:g.75963455C>G
  • NG_011715.1:g.23295G>C
  • NM_001329938.2:c.787G>C
  • NM_001329939.2:c.787G>C
  • NM_003239.5:c.787G>CMANE SELECT
  • NP_001316867.1:p.Asp263His
  • NP_001316868.1:p.Asp263His
  • NP_003230.1:p.Asp263His
  • LRG_399t1:c.787G>C
  • LRG_399:g.23295G>C
  • NC_000014.8:g.76429798C>G
  • NM_003239.2:c.787G>C
  • p.(Asp263His)
Protein change:
D263H; ASP263HIS
Links:
OMIM: 190230.0008; dbSNP: rs796051886
NCBI 1000 Genomes Browser:
rs796051886
Molecular consequence:
  • NM_001329938.2:c.787G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001329939.2:c.787G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003239.5:c.787G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Rienhoff syndrome
Synonyms:
Loeys-Dietz syndrome 5
Identifiers:
MONDO: MONDO:0014262; MedGen: C3810012; OMIM: 615582

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000238547OMIM
no assertion criteria provided
Pathogenic
(Apr 7, 2015) 		germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Mutations in a TGF-β ligand, TGFB3, cause syndromic aortic aneurysms and dissections.

Bertoli-Avella AM, Gillis E, Morisaki H, Verhagen JMA, de Graaf BM, van de Beek G, Gallo E, Kruithof BPT, Venselaar H, Myers LA, Laga S, Doyle AJ, Oswald G, van Cappellen GWA, Yamanaka I, van der Helm RM, Beverloo B, de Klein A, Pardo L, Lammens M, Evers C, Devriendt K, et al.

J Am Coll Cardiol. 2015 Apr 7;65(13):1324-1336. doi: 10.1016/j.jacc.2015.01.040.

PubMed [citation]
PMID:
25835445
PMCID:
PMC4380321

Details of each submission

From OMIM, SCV000238547.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a 31-year-old man who had thoracic aortic aneurysm dissection (TAAD) at age 30 with a 70-mm aortic root and who also exhibited dolichocephaly, high-arched palate, severe retrognathia, delayed puberty, and short stature (LDS5; 615582), Bertoli-Avella et al. (2015) identified heterozygosity for a c.787G-C transversion (c.787G-C, NM_003239.2) in exon 5 of the TGFB3 gene, resulting in an asp263-to-his (D263H) substitution at a highly conserved residue in the RGD motif of the LAP domain. The mutation was present in his 70-year-old maternal aunt, who had a 38-mm aortic sinus diameter and mild mitral insufficiency; it was also found in his 64-year-old mother, who had mild mitral insufficiency but an aortic sinus diameter of only 34 mm, and in his asymptomatic 34-year-old brother, who had an aortic sinus diameter of 32 mm. Microscopic examination of the proband's dissected aortic wall showed elastic fiber fragmentation with higher collagen and proteoglycan deposition. Immunohistochemical analysis of aortic tissue showed paradoxically enhanced TGF-beta (TGFB1; 190180) signaling, as shown by increased levels of SMAD2 (601366) and ERK (see 601795) as well as elevated TGFB1 mRNA.

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

Last Updated: Dec 11, 2022