TNNC1
troponin C1, slow skeletal and cardiac type, the group of Troponin complex subunits|EF-hand domain containing
Basic information
Region (hg38): 3:52451100-52454041
Previous symbols: [ "TNNC" ]
Links
Phenotypes
GenCC
Source:
- hypertrophic cardiomyopathy 13 (Moderate), mode of inheritance: AD
- dilated cardiomyopathy 1Z (Moderate), mode of inheritance: AD
- familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
- dilated cardiomyopathy 1Z (Definitive), mode of inheritance: AD
- dilated cardiomyopathy 1Z (Strong), mode of inheritance: AD
- hypertrophic cardiomyopathy 13 (Strong), mode of inheritance: AD
- hypertrophic cardiomyopathy (Definitive), mode of inheritance: AD
- dilated cardiomyopathy (Definitive), mode of inheritance: AD
- arrhythmogenic right ventricular cardiomyopathy (No Known Disease Relationship), mode of inheritance: AD
- hypertrophic cardiomyopathy 13 (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Cardiomyopathy, familial hypertrophic 13; Cardiomyopathy, dilated, 1Z | AD | Cardiovascular | Preventive measures, surveillance (eg, including echocardiography and electrocardiography), and medical management may be helpful to help decrease morbidity; Cardiac transplantation has been reported | Cardiovascular | 11385718; 15542288; 18572189 |
ClinVar
This is a list of variants' phenotypes submitted to
- Dilated_cardiomyopathy_1Z (289 variants)
- Hypertrophic_cardiomyopathy_13 (282 variants)
- Cardiovascular_phenotype (108 variants)
- not_provided (70 variants)
- not_specified (50 variants)
- Cardiomyopathy (25 variants)
- TNNC1-related_disorder (9 variants)
- Primary_dilated_cardiomyopathy (3 variants)
- Hypertrophic_cardiomyopathy (3 variants)
- Dilated_cardiomyopathy_1S (2 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the TNNC1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003280.3. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 75 | 78 | ||||
| missense | 11 | 154 | 169 | |||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 12 | 12 | ||||
| splice donor/acceptor (+/-2bp) | 6 | |||||
| Total | 5 | 11 | 174 | 75 | 1 |
Highest pathogenic variant AF is 0.000019206725
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| TNNC1 | protein_coding | protein_coding | ENST00000232975 | 6 | 2969 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.678 | 0.318 | 125709 | 0 | 8 | 125717 | 0.0000318 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.77 | 48 | 97.0 | 0.495 | 0.00000639 | 1106 |
| Missense in Polyphen | 20 | 49.077 | 0.40753 | 550 | ||
| Synonymous | -0.736 | 45 | 39.1 | 1.15 | 0.00000332 | 263 |
| Loss of Function | 2.29 | 1 | 7.99 | 0.125 | 3.53e-7 | 104 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000145 | 0.000145 |
| Ashkenazi Jewish | 0.0000993 | 0.0000992 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000112 | 0.00000879 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components: Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the inhibitory action of Tn on actin filaments.;
- Disease
- DISEASE: Cardiomyopathy, dilated 1Z (CMD1Z) [MIM:611879]: 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:15542288}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, familial hypertrophic 13 (CMH13) [MIM:613243]: 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:11385718, ECO:0000269|PubMed:16302972, ECO:0000269|PubMed:18572189, ECO:0000269|PubMed:19439414}. 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);Calcium 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;MFAP5-mediated ovarian cancer cell motility and invasiveness;Striated Muscle Contraction;Striated Muscle Contraction;Muscle contraction
(Consensus)
Recessive Scores
- pRec
- 0.236
Intolerance Scores
- loftool
- 0.220
- rvis_EVS
- -0.19
- rvis_percentile_EVS
- 39.68
Haploinsufficiency Scores
- pHI
- 0.0970
- hipred
- Y
- hipred_score
- 0.555
- ghis
- 0.615
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.801
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Medium |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Tnnc1
- Phenotype
Zebrafish Information Network
- Gene name
- tnnc1a
- Affected structure
- cardiac muscle cell
- Phenotype tag
- abnormal
- Phenotype quality
- disorganized
Gene ontology
- Biological process
- diaphragm contraction;skeletal muscle contraction;regulation of muscle contraction;response to metal ion;transition between fast and slow fiber;muscle filament sliding;regulation of muscle filament sliding speed;regulation of ATPase activity;ventricular cardiac muscle tissue morphogenesis;cardiac muscle contraction
- Cellular component
- cytosol;troponin complex;cardiac Troponin complex
- Molecular function
- calcium ion binding;protein binding;troponin I binding;troponin T binding;protein homodimerization activity;calcium-dependent protein binding;actin filament binding