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rs3729547

From SNPedia

Orientationminus
Stabilizedminus
Geno Mag Summary
(C;C) 0 common in clinvar
Make rs3729547(C;T)
Make rs3729547(T;T)
ReferenceGRCh38 38.1/141
Chromosome1
Position201365254
GeneTNNT2
is asnp
is mentioned by
dbSNPrs3729547
ebirs3729547
HLIrs3729547
Exacrs3729547
Varsomers3729547
Maprs3729547
PheGenIrs3729547
hapmaprs3729547
1000 genomesrs3729547
hgdprs3729547
ensemblrs3729547
gopubmedrs3729547
geneviewrs3729547
scholarrs3729547
googlers3729547
pharmgkbrs3729547
gwascentralrs3729547
openSNPrs3729547
23andMers3729547
23andMe allrs3729547
SNP Nexus

SNPshotrs3729547
SNPdbers3729547
MSV3drs3729547
GWAS Ctlgrs3729547
GMAF0.3283
Max Magnitude0
? (C;C) (C;T) (T;T) 28
rs3729547, is a SNP that was recently shown to be mildly associated with dilated cardiomyopathy (DCM) in the Han Chinese population and hypertrophic cardiomyopathy in the Indian population. [PMID 23586019OA-icon.png] [PMID 22017532]. This SNP is located within the coding sequence of the TNNT2 gene, which encodes a component of the troponin complex critical for proper sarcomeric contractility in cardiomyocytes, the cell type driving contraction in the heart. [PMID 11239412]

A number of earlier studies have shown that mutations in TNNT2 can lead to dilated cardiomyopathy. [PMID 20031601OA-icon.png] [PMID 20978592OA-icon.png] [PMID 11779518‎] characterized by a thinning of the ventricular wall, or conversely, hypertrophic cardiomyopathy (HCM), characterized by a thickening of the ventricular wall. Both conditions lead to an overall weakening of the heart muscle and can lead to heart failure or sudden cardiac death. [PMID 11239412] The molecular mechanisms whereby mutations in the same gene (TNNT2) can lead to two diseases (DCM and HCM) with such contrasting phenotypes are still not well-understood.

In a study by Li et al, rs3729547 (C to T) and another tagging SNP also in TNNT2, rs3729843 (G to A), were shown to be associated with DCM in a cohort of Han Chinese individuals (X2= 6.63, P = 0.036; X2 = 9.787, P = 0.008, respectively) The risk allele for rs3729547 is T and the risk allele for rs3729843 is A. rs3729547 is a synonymous (isoleucine) variant whereas rs3729843 is a noncoding SNP. In this study, the authors investigated the association between 10 tagging SNPs (these two included) and DCM using matrix-assisted laser desorption/ionization, time-of-flight mass spectrometry (MALDI-TOF-MS). However, the patients from this study were all members of the Han Chinese population, and therefore, these SNPs must be studied in the context of another ethnic group to validate strong associations between these SNPs and DCM. Additionally, this study was limited by its sample size, as only 97 DCM patients and 189 healthy unrelated controls partook in this study. [PMID 23586019OA-icon.png]

In a second study published by Rani et al, the TNNT2 gene was sequenced in 162 patients with hypertrophic cardiomyopathy (HCM) and in 179 healthy controls. HCM phenotype ranged from moderate to severe, but a limited number of corrective operations were performed in these HCM patients. In contrast to the Li et al paper, this study was conducted exclusively in patients from India. Fifteen associated variants were uncovered, including rs3729547 (C to T) and rs3729843 (G to A), which were found to be in high linkage disequilibrium in the HCM patients. They also identified a 5bp deletion polymorphism in this Indian population that was previously shown to be associated with HCM patients of French, Spanish, and Japanese origin. [PMID 20978592OA-icon.png]

OMIM191045
DescTROPONIN T2, CARDIAC; TNNT2
Variant
Relatedalso
[PMID 23586019OA-icon.png] Tnnt2 gene polymorphisms are associated with susceptibility to idiopathic dilated cardiomyopathy in the han chinese population.


[PMID 22017532] Cardiac troponin t (tnnt2) mutations are less prevalent in indian hypertrophic cardiomyopathy patients.


[PMID 11239412] The genetic basis for cardiomyopathy: From mutation identification to mechanistic paradigms.


[PMID 20031601OA-icon.png] Clinical and functional characterization of tnnt2 mutations identified in patients with dilated cardiomyopathy


[PMID 20978592OA-icon.png] Recurrent and founder mutations in the netherlands: Mutation p.K217del in troponin t2, causing dilated cardiomyopathy.


[PMID 11779518] A novel mutation lys273glu in the cardiac troponin t gene shows high degree of penetrance and transition from hypertrophic to dilated cardiomyopathy.


ClinVar
Risk rs3729547(G,T;G,T)
Alt rs3729547(G,T;G,T)
Reference rs3729547(C;C)
Significance Non-pathogenic
Disease not specified
Variation info
Gene TNNT2
CLNDBN not specified
Reversed 1
HGVS NC_000001.10:g.201334382G>A; NC_000001.10:g.201334382G>C
CLNSRC ClinVar GeneDx
CLNACC RCV000036579.3, RCV000168966.1,



[PMID 20592870OA-icon.png] Comparison of the Illumina Genome Analyzer and Roche 454 GS FLX for resequencing of hypertrophic cardiomyopathy-associated genes.


[PMID 26400351] Significance of sarcomere gene mutation in patients with dilated cardiomyopathy