TGFB1 T263I - GET-Evidence

Curation:
Currentness:

TGFB1 T263I

(TGFB1 Thr263Ile)


Short summary

Carriers may be less likely to have cleft lip and palate congenital deformity.

Variant evidence
Computational -
Functional -
Case/Control

Case control data for this variant alone is insufficient to establish significance

See Stoll C et al. 2004 (15212689).

Familial

No familial data

 
Clinical importance
Severity 3
Treatability 4

Treatable with surgery

Penetrance

~0.07% reduced risk of cleft palate (estimate: .1% in general population, .03% for carriers)

 

Impact

Low clinical importance, Uncertain protective

(The "low clinical importance, uncertain" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

dominant

Summary of published research, and additional commentary

 

Allele frequency

  • A @ chr19:41847860: 2.1% (221/10758) in EVS
  • A @ chr19:46539699: 3.1% (4/128) in GET-Evidence
  • Frequency shown in summary reports: 2.1% (221/10758)

Publications
 

Stoll C, Mengsteab S, Stoll D, Riediger D, Gressner AM, Weiskirchen R. Analysis of polymorphic TGFB1 codons 10, 25, and 263 in a German patient group with non-syndromic cleft lip, alveolus, and palate compared with healthy adults. BMC Med Genet. 2004 Jun 22;5:15. PubMed PMID: 15212689; PubMed Central PMCID: PMC441379.

2 / 60 patients with cleft palate had this variant, while 6 / 60 control subjects had it. This is not a statistically significant difference in itself.

Another variant in the same gene, Arg25Pro, was found in 2/60 patients and 10/60 controls (p=0.0295 with two-tailed fisher’s exact), and combined data for the two (4/60 vs. 15/60 with either) has p=0.011.

The authors conclude that these variants may be protective by causing lower TGF-β1 concentration, and that cleft palate may be associated with increased concentration (thus these would be protective variants).

Genomes
 

hu0E64A1 - CGI sample GS01173-DNA_B02 from PGP sample 94378523
het A @ chr19:41847860

 

 

huAE6220 - CGI sample GS00253-DNA_H01_200_37
het A @ chr19:41847860

 

huBEDA0B - CGI sample GS00253-DNA_C01_200_37
het A @ chr19:41847860

 

GS10851 - var-GS10851-1100-36-ASM
het A @ chr19:46539700

 

Other external references
 

    dbSNP
  • rs1800472
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    Web search results (49 hits -- see all)
  • BioMed Central | Full text | Transforming growth factor beta ...
    Transforming growth factor beta-1 (TGFB1) and peak bone mass: association ... Homozygous knock-out of the TGFB1 gene in mice is associated with an osteopenic ...
    www.biomedcentral.com/1471-2474/6/29
  • GeneCanvas
    TGFB1/C-509T. TGFB1/C-988A. TGFB1/G-800A. TGFB1/L10P. TGFB1/R25P. TGFB1/T263I. TGFB3/T-24/in4C. TLR4/D299G. TLR4/T399I. TNF/+325/in1 ins/del. TNF/-869ins/del. TNF/C-857T ...
    genecanvas.idf.inserm.fr/infusions/.../PolymorphismsList.php
  • Publications Search
    Search of Publications Database for the Division of Cancer Epidemiology and Genetics (DCEG) of the National Cancer Institute (NCI), National Institutes of Health (NIH)
    dceg2.cancer.gov/cgi-bin-pubsearch/pubsearch/index.pl?...
  • Thyroid nodules, polymorphic variants in DNA repair and RET ...
    sigurdsa@mail.nih.gov Risk factors for thyroid cancer remain largely unknown except for ionizing radiation ... (rs1799782, P trend = 0.03) and TGFB1 T263I (rs1800472, P = 0.009) ...
    www.ncbi.nlm.nih.gov/pubmed/19138047
  • BMC Musculoskeletal Disorders
    Abundant in bone matrix [10], secreted TGFB1 is an. important regulator of osteoblast ... Polymorphic loci of the TGFB1 gene. Each locus (A to G) is shown in ...
    www.biomedcentral.com/content/pdf/1471-2474-6-29.pdf
  • Association of Genetic Variation in the Transforming Growth ...
    The T263I single-nucleotide poly- morphism (SNP) is located in the pro-protein portion of ... in TGFB1 and use the data from two case-control studies to clarify ...
    cancerres.aacrjournals.org/cgi/reprint/68/4/1236.pdf
  • Land, CE (Charles E)
    Land, CE (Charles E) :: Uncertainty, low-dose extrapolation and the threshold hypothesis. ... (rs1799782, P trend = 0.03) and TGFB1 T263I (rs1800472, P = 0.009). Similar patterns ...
    lib.bioinfo.pl/auid:72009
  • Association of Genetic Variation in the Transforming Growth ...
    The T263I single-nucleotide polymorphism (SNP) is located in the pro-protein portion of ... Genetic variation at the TGFB1 locus. Table 1 lists the 26 SNPs, ...
    cancerres.aacrjournals.org/cgi/content/full/68/4/1236
  • The Transforming Growth Factor {beta}1 Promoter Polymorphism ...
    Transforming growth factor 1 (TGFB1) is increased in the lungs of asthmatics and may modulate airway ... The coding polymorphism T263I in TGF-{beta}1 is associated with ...
    ajrccm.atsjournals.org/cgi/content/short/200307-973OCv1
  • The coding polymorphism T263I in TGF-{beta}1 is associated ...
    The coding polymorphism T263I in TGF-ß1 is associated with ... conclude that TGFB1 influences the susceptibility for otosclerosis, and that the I263 ...
    hmg.oxfordjournals.org/cgi/content/short/ddm150v1

Other in silico analyses
 

  • NBLOSUM100 score = 3
  • GET-Evidence autoscore = 5

Edit history
 

Gene search

"GENE" or "GENE A123C":

Log in