GeneBe

TNNI3

troponin I3, cardiac type, the group of Troponin complex subunits

Basic information

Region (hg38): 19:55151767-55157773

Previous symbols: [ "CMD2A" ]

Links

ENSG00000129991 ∙ NCBI:7137 ∙ OMIM:191044 ∙ HGNC:11947 ∙ Uniprot:P19429 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • hypertrophic cardiomyopathy 7 (Strong), mode of inheritance: AD
  • hypertrophic cardiomyopathy 7 (Strong), mode of inheritance: AR
  • familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
  • familial isolated restrictive cardiomyopathy (Supportive), mode of inheritance: AD
  • dilated cardiomyopathy 2A (Definitive), mode of inheritance: AR
  • hypertrophic cardiomyopathy 7 (Definitive), mode of inheritance: AD
  • cardiomyopathy, familial restrictive, 1 (Strong), mode of inheritance: AD
  • dilated cardiomyopathy 1FF (Strong), mode of inheritance: AD
  • dilated cardiomyopathy 2A (Strong), mode of inheritance: AR
  • hypertrophic cardiomyopathy 7 (Strong), mode of inheritance: AD
  • arrhythmogenic right ventricular cardiomyopathy (No Known Disease Relationship), mode of inheritance: AD
  • hypertrophic cardiomyopathy (Definitive), mode of inheritance: AD
  • dilated cardiomyopathy (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Cardiomyopathy, familial hypertrophic 7; Cardiomyopathy, dilated 1FF; Cardiomyopathy, dilated, 2A; Cardiomyopathy, familial restrictive 1AD/ARCardiovascularPreventive measures, surveillance (eg, including echocardiography and electrocardiography), and medical management may be helpful to decrease morbidity; Cardiac transplantation has been reportedCardiovascular3594932; 9241277; 9753711; 12531876; 15070570; 16267253; 19590045; 20569525; 21846512; 22301726; 22455086; 22876777; 23349452; 23396983; 23906401

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TNNI3 gene.

  • Hypertrophic_cardiomyopathy (552 variants)
  • Cardiomyopathy (211 variants)
  • Cardiovascular_phenotype (201 variants)
  • not_provided (167 variants)
  • not_specified (96 variants)
  • Hypertrophic_cardiomyopathy_7 (72 variants)
  • Cardiomyopathy,_familial_restrictive,_1 (51 variants)
  • Dilated_cardiomyopathy_2A (46 variants)
  • Dilated_cardiomyopathy_1FF (36 variants)
  • Familial_Hypertrophic_Cardiomyopathy_with_Wolff-Parkinson-White_Syndrome (18 variants)
  • TNNI3-related_disorder (13 variants)
  • Primary_familial_hypertrophic_cardiomyopathy (12 variants)
  • Primary_dilated_cardiomyopathy (10 variants)
  • Familial_restrictive_cardiomyopathy (7 variants)
  • Restrictive_cardiomyopathy (6 variants)
  • Dilated_Cardiomyopathy,_Recessive (6 variants)
  • Hypertrophic_cardiomyopathy_1 (5 variants)
  • SUDDEN_INFANT_DEATH_SYNDROME (3 variants)
  • Dilated_cardiomyopathy_1A (1 variants)
  • Amyloidosis,_hereditary_systemic_1 (1 variants)
  • Left_ventricular_noncompaction_cardiomyopathy (1 variants)
  • Long_QT_syndrome (1 variants)
  • Primary_familial_dilated_cardiomyopathy (1 variants)
  • Myocarditis (1 variants)
  • TNNI3-associated_disorder (1 variants)
  • Primary_ciliary_dyskinesia (1 variants)
  • Sudden_cardiac_arrest (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TNNI3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000363.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
4
clinvar
124
clinvar
1
clinvar
 129
missense
20
clinvar
53
clinvar
296
clinvar
8
clinvar
1
clinvar
 378
nonsense
5
clinvar
5
clinvar
8
clinvar
 18
start loss
2
 2
frameshift
4
clinvar
6
clinvar
16
clinvar
 26
splice donor/acceptor (+/-2bp)
14
clinvar
6
clinvar
 20
Total 29 78 332 132 2

Highest pathogenic variant AF is 0.000029758

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
TNNI3protein_codingprotein_codingENST00000344887 86005
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.09630.8971247650331247980.000132
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.28891300.6840.000008511338
Missense in Polyphen2543.1090.57993448
Synonymous-0.4415652.01.080.00000308415
Loss of Function2.35413.20.3037.23e-7147

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0003290.000306
Ashkenazi Jewish0.000.00
East Asian0.00005560.0000556
Finnish0.00004640.0000464
European (Non-Finnish)0.0001610.000159
Middle Eastern0.00005560.0000556
South Asian0.00009870.0000980
Other0.0003300.000330

dbNSFP

Source: dbNSFP

Function
FUNCTION: Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.;
Disease
DISEASE: Cardiomyopathy, familial hypertrophic 7 (CMH7) [MIM:613690]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. {ECO:0000269|PubMed:11815426, ECO:0000269|PubMed:12707239, ECO:0000269|PubMed:12974739, ECO:0000269|PubMed:16199542, ECO:0000269|PubMed:9241277}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, familial restrictive 1 (RCM1) [MIM:115210]: A heart disorder characterized by impaired filling of the ventricles with reduced diastolic volume, in the presence of normal or near normal wall thickness and systolic function. {ECO:0000269|PubMed:12531876}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, dilated 2A (CMD2A) [MIM:611880]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:15070570}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, dilated 1FF (CMD1FF) [MIM:613286]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:19590045, ECO:0000269|PubMed:21846512}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Cardiac muscle contraction - Homo sapiens (human);Dilated cardiomyopathy (DCM) - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Disopyramide Action Pathway;Procainamide (Antiarrhythmic) Action Pathway;Phenytoin (Antiarrhythmic) Action Pathway;Fosphenytoin (Antiarrhythmic) Action Pathway;Bopindolol Action Pathway;Timolol Action Pathway;Carteolol Action Pathway;Bevantolol Action Pathway;Practolol Action Pathway;Dobutamine Action Pathway;Isoprenaline Action Pathway;Arbutamine Action Pathway;Amiodarone Action Pathway;Levobunolol Action Pathway;Metipranolol Action Pathway;Mexiletine Action Pathway;Lidocaine (Antiarrhythmic) Action Pathway;Quinidine Action Pathway;Sotalol Action Pathway;Epinephrine Action Pathway;Betaxolol Action Pathway;Atenolol Action Pathway;Alprenolol Action Pathway;Acebutolol Action Pathway;Muscle/Heart Contraction;Diltiazem Action Pathway;Propranolol Action Pathway;Pindolol Action Pathway;Penbutolol Action Pathway;Oxprenolol Action Pathway;Metoprolol Action Pathway;Esmolol Action Pathway;Bisoprolol Action Pathway;Bupranolol Action Pathway;Nebivolol Action Pathway;Amlodipine Action Pathway;Verapamil Action Pathway;Nitrendipine Action Pathway;Nisoldipine Action Pathway;Nimodipine Action Pathway;Ibutilide Action Pathway;Tocainide Action Pathway;Flecainide Action Pathway;Isradipine Action Pathway;Nifedipine Action Pathway;Felodipine Action Pathway;Nadolol Action Pathway;Carvedilol Action Pathway;Labetalol Action Pathway;Cardiac Progenitor Differentiation;Striated Muscle Contraction;Ion homeostasis;Striated Muscle Contraction;Cardiac conduction;Muscle contraction (Consensus)

Recessive Scores

pRec
0.382

Intolerance Scores

loftool
rvis_EVS
0.15
rvis_percentile_EVS
64.11

Haploinsufficiency Scores

pHI
0.625
hipred
Y
hipred_score
0.659
ghis
0.403

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.826

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Tnni3
Phenotype
cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; muscle phenotype;

Gene ontology

Biological process
vasculogenesis;regulation of systemic arterial blood pressure by ischemic conditions;skeletal muscle contraction;cellular calcium ion homeostasis;muscle contraction;regulation of smooth muscle contraction;heart development;regulation of cardiac muscle contraction by calcium ion signaling;muscle filament sliding;negative regulation of ATPase activity;ventricular cardiac muscle tissue morphogenesis;heart contraction;cardiac muscle contraction
Cellular component
cytosol;troponin complex;sarcomere;cardiac myofibril;cardiac Troponin complex
Molecular function
actin binding;protein binding;calcium channel inhibitor activity;protein kinase binding;protein domain specific binding;troponin C binding;troponin T binding;metal ion binding;calcium-dependent protein binding;actin filament binding