|
Hypertrophic Cardiomyopathy
|
|
0.740 |
GeneticVariation
|
BEFREE |
We recently reported that introduction of an HCM-associated mutation in either inhibitory-peptide (cTnI(R146G)) or cardiac-specific N-terminus (cTnI(R21C)) of cTnI blunts the PKA-mediated modulation on myofibril activation/relaxation kinetics by prohibiting formation of intrasubunit contacts between these regions.
|
27150586 |
2016 |
|
Cardiomyopathy, Hypertrophic, Familial
|
|
0.730 |
GeneticVariation
|
BEFREE |
We investigated the effects of two mutations in human cardiac troponin I, Arg(145)-->Gly and Gly(203)-->Ser, that are reported to cause familial hypertrophic cardiomyopathy.
|
11853553 |
2002 |
|
Cardiomyopathy, Hypertrophic, Familial
|
|
0.730 |
GeneticVariation
|
BEFREE |
We have analyzed the functional effects of two HCM mutations (R145G and R162W) using purified recombinant cTnI.
|
10806205 |
2000 |
|
Hypertrophic Cardiomyopathy
|
|
0.740 |
CausalMutation
|
CLINVAR |
Two mutations in troponin I that cause hypertrophic cardiomyopathy have contrasting effects on cardiac muscle contractility.
|
11853553 |
2002 |
|
Hypertrophic Cardiomyopathy
|
|
0.740 |
CausalMutation
|
CLINVAR |
To determine whether five mutations in cTnI (L144Q, R145W, A171T, K178E, and R192H) associated with restrictive cardiomyopathy were distinguishable from hypertrophic cardiomyopathy-causing mutations in cTnI, actomyosin ATPase activity and skinned fiber studies were carried out.
|
15961398 |
2005 |
|
Hyperlipoproteinemia Type IIa
|
|
0.010 |
GeneticVariation
|
BEFREE |
Thus, while the FHC mutation R144G enhances the effect of T142 phosphorylation on the interaction of cIp and cCTnC.2Ca(2+), the FHC mutation R161W suppresses the effect of S149 phosphorylation on the interaction of cSp and cNTnC.Ca(2+), demonstrating linkages between the FHC mutation and phosphorylation of cTnI.
|
14661957 |
2003 |
|
Hypertrophic Cardiomyopathy
|
|
0.740 |
CausalMutation
|
CLINVAR |
These results suggest that the phenotype of hypertrophic cardiomyopathy is most likely caused by the compensatory mechanisms in the cardiovascular system that are activated by 1) higher energy cost in the heart resulting from a significant decrease in average force per cross-bridge, 2) slowed relaxation (diastolic dysfunction) caused by prolonged [Ca(2+)] and force transients, and 3) an inability of the cardiac TnI to completely inhibit activation in the absence of Ca(2+) in Tg-R145G mice.
|
18430738 |
2008 |
|
Hypertrophic Cardiomyopathy
|
|
0.740 |
GeneticVariation
|
BEFREE |
These results suggest that the phenotype of hypertrophic cardiomyopathy is most likely caused by the compensatory mechanisms in the cardiovascular system that are activated by 1) higher energy cost in the heart resulting from a significant decrease in average force per cross-bridge, 2) slowed relaxation (diastolic dysfunction) caused by prolonged [Ca(2+)] and force transients, and 3) an inability of the cardiac TnI to completely inhibit activation in the absence of Ca(2+) in Tg-R145G mice.
|
18430738 |
2008 |
|
Hypertrophic obstructive cardiomyopathy
|
|
0.010 |
GeneticVariation
|
BEFREE |
These results suggest that the phenotype of hypertrophic cardiomyopathy is most likely caused by the compensatory mechanisms in the cardiovascular system that are activated by 1) higher energy cost in the heart resulting from a significant decrease in average force per cross-bridge, 2) slowed relaxation (diastolic dysfunction) caused by prolonged [Ca(2+)] and force transients, and 3) an inability of the cardiac TnI to completely inhibit activation in the absence of Ca(2+) in Tg-R145G mice.
|
18430738 |
2008 |
|
Restrictive cardiomyopathy
|
|
0.020 |
GeneticVariation
|
BEFREE |
These perturbed biophysical and biochemical myofilament properties are likely to significantly contribute to the diastolic cardiac pump dysfunction that is seen in patients suffering from a restrictive cardiomyopathy that is associated with the cTnI R145W mutation.
|
27557662 |
2016 |
|
CARDIOMYOPATHY, FAMILIAL RESTRICTIVE, 1 (disorder)
|
|
0.810 |
GeneticVariation
|
BEFREE |
These results suggest that the RCM-associated cTnI R145W mutation induces a permanent structural state that is similar to, but more extensive than, that induced by PKC-mediated phosphorylation of cTnI Thr-143.
|
27557662 |
2016 |
|
Hypertrophic Cardiomyopathy
|
|
0.740 |
CausalMutation
|
CLINVAR |
The role of electrostatics in the interaction of the inhibitory region of troponin I with troponin C.
|
16274223 |
2005 |
|
Cardiomyopathy, Hypertrophic, Familial
|
|
0.730 |
GeneticVariation
|
BEFREE |
The near N-terminal region (cRp; residues 34-71) contains the protein kinase C (PKC) phosphorylation sites S41 and S43, the inhibitory region (cIp; residues 128-147) contains another PKC site T142 and a familial hypertrophic cardiomyopathy (FHC) mutation R144G, and the switch region (cSp; residues 147-163) contains the novel p21-activated kinase (PAK) site S149 and another FHC mutation R161W.
|
14661957 |
2003 |
|
Hypertrophic Cardiomyopathy
|
|
0.740 |
GeneticVariation
|
BEFREE |
The heightened Ca2+ sensitivity of force found with hypertrophic cardiomyopathy (HCM)-associated mutant cardiac troponin I (cTnIR145G; R146G in rodents) has been postulated to be an underlying cause of hypertrophic growth and premature sudden death in humans and in animal models of the disease.
|
12242271 |
2002 |
|
Cardiomyopathy, Hypertrophic, Familial
|
|
0.730 |
CausalMutation
|
CLINVAR |
Some cardiomyopathy-causing troponin I mutations stabilize a functional intermediate actin state.
|
19289050 |
2009 |
|
CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 7
|
|
0.800 |
GeneticVariation
|
UNIPROT |
Sarcomere protein gene mutations in hypertrophic cardiomyopathy of the elderly.
|
11815426 |
2002 |
|
Hypertrophic Cardiomyopathy
|
|
0.740 |
CausalMutation
|
CLINVAR |
Restrictive Cardiomyopathy Troponin I R145W Mutation Does Not Perturb Myofilament Length-dependent Activation in Human Cardiac Sarcomeres.
|
27557662 |
2016 |
|
Cardiomyopathy, Hypertrophic, Familial
|
|
0.730 |
CausalMutation
|
CLINVAR |
Restrictive Cardiomyopathy Troponin I R145W Mutation Does Not Perturb Myofilament Length-dependent Activation in Human Cardiac Sarcomeres.
|
27557662 |
2016 |
|
Hypertrophic Cardiomyopathy
|
|
0.740 |
CausalMutation
|
CLINVAR |
Reduced peak current of L-type Ca(2+) channel in cells transduced with cTnI R146W might contribute to the disease-causing mechanism of this mutation in patients with hypertrophic cardiomyopathy.
|
18269819 |
2007 |
|
Hypertrophic Cardiomyopathy
|
|
0.740 |
CausalMutation
|
CLINVAR |
Recurrent and founder mutations in the Netherlands: cardiac Troponin I (TNNI3) gene mutations as a cause of severe forms of hypertrophic and restrictive cardiomyopathy.
|
21533915 |
2011 |
|
Cardiomyopathy, Hypertrophic, Familial
|
|
0.730 |
CausalMutation
|
CLINVAR |
Recurrent and founder mutations in the Netherlands: cardiac Troponin I (TNNI3) gene mutations as a cause of severe forms of hypertrophic and restrictive cardiomyopathy.
|
21533915 |
2011 |
|
CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 7
|
|
0.800 |
GeneticVariation
|
UNIPROT |
Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics.
|
27854360 |
2017 |
|
Cardiomyopathy, Hypertrophic, Familial
|
|
0.730 |
CausalMutation
|
CLINVAR |
Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.
|
27532257 |
2017 |
|
Hypertrophic Cardiomyopathy
|
|
0.740 |
CausalMutation
|
CLINVAR |
Prevalence, clinical significance, and genetic basis of hypertrophic cardiomyopathy with restrictive phenotype.
|
17599605 |
2007 |
|
Hypertrophic Cardiomyopathy
|
|
0.740 |
CausalMutation
|
CLINVAR |
Myocardial late gadolinium enhancement cardiovascular magnetic resonance in hypertrophic cardiomyopathy caused by mutations in troponin I.
|
16020591 |
2005 |