TNNC1

troponin C1, slow skeletal and cardiac type, the group of Troponin complex subunits|EF-hand domain containing

Basic information

Region (hg38): 3:52451099-52454041

Previous symbols: [ "TNNC" ]

Links

ENSG00000114854 ∙ NCBI:7134 ∙ OMIM:191040 ∙ HGNC:11943 ∙ Uniprot:P63316 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the TNNC1 gene.

• Dilated cardiomyopathy 1Z;Hypertrophic cardiomyopathy 13 (139 variants)
• Hypertrophic cardiomyopathy 13;Dilated cardiomyopathy 1Z (78 variants)
• Cardiovascular phenotype (68 variants)
• not provided (66 variants)
• not specified (43 variants)
• Cardiomyopathy (24 variants)
• Dilated cardiomyopathy 1Z (20 variants)
• Hypertrophic cardiomyopathy 13 (18 variants)
• TNNC1-related condition (3 variants)
• Hypertrophic cardiomyopathy (3 variants)
• Dilated cardiomyopathy 1S (2 variants)
• Primary dilated cardiomyopathy (2 variants)
• Inborn genetic diseases (1 variants)
• Left ventricular noncompaction cardiomyopathy (1 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	48		50
missense		8	122			130
nonsense			1			1
start loss						0
frameshift			7			7
inframe indel			3			3
splice donor/acceptor (+/-2bp)			5			5
splice region			9	10		19
non coding			8	27	5	40
Total	0	8	148	75	5

Variants in TNNC1

This is a list of pathogenic ClinVar variants found in the TNNC1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-52451148-G-A		Hypertrophic cardiomyopathy 13 • Dilated cardiomyopathy 1Z	Conflicting classifications of pathogenicity (Jan 13, 2018)
3-52451152-C-T			Benign (Mar 03, 2015)
3-52451192-T-G		Hypertrophic cardiomyopathy 13 • Dilated cardiomyopathy 1Z	Benign/Likely benign (Jan 13, 2018)
3-52451198-C-A			Benign (Mar 03, 2015)
3-52451200-C-T		Dilated cardiomyopathy 1Z • Hypertrophic cardiomyopathy 13 • Dilated cardiomyopathy 1Z;Hypertrophic cardiomyopathy 13	Uncertain significance (Aug 20, 2021)
3-52451267-G-A		TNNC1-related disorder	Conflicting classifications of pathogenicity (Apr 13, 2020)
3-52451275-C-A		Cardiomyopathy	Uncertain significance (Jun 21, 2023)
3-52451278-C-T		Dilated cardiomyopathy 1Z;Hypertrophic cardiomyopathy 13	Likely benign (May 31, 2023)
3-52451281-C-T		not specified • Dilated cardiomyopathy 1Z;Hypertrophic cardiomyopathy 13	Likely benign (Jul 20, 2020)
3-52451285-C-T		Dilated cardiomyopathy 1Z	Likely pathogenic (Jan 13, 2020)
3-52451287-C-T		Hypertrophic cardiomyopathy 13;Dilated cardiomyopathy 1Z • Cardiovascular phenotype	Likely benign (Nov 20, 2023)
3-52451288-T-C		Hypertrophic cardiomyopathy 13;Dilated cardiomyopathy 1Z	Uncertain significance (Aug 21, 2021)
3-52451288-T-G		Dilated cardiomyopathy 1Z;Hypertrophic cardiomyopathy 13	Uncertain significance (May 22, 2017)
3-52451291-A-C		Hypertrophic cardiomyopathy 13;Dilated cardiomyopathy 1Z	Uncertain significance (Jul 28, 2021)
3-52451292-T-A		Primary dilated cardiomyopathy • Dilated cardiomyopathy 1Z;Hypertrophic cardiomyopathy 13	Uncertain significance (Apr 08, 2023)
3-52451292-T-C		Dilated cardiomyopathy 1Z	Uncertain significance (Oct 18, 2021)
3-52451292-T-G		Dilated cardiomyopathy 1Z;Hypertrophic cardiomyopathy 13 • Cardiovascular phenotype	Uncertain significance (Dec 09, 2023)
3-52451305-C-G		Cardiovascular phenotype	Uncertain significance (Nov 15, 2022)
3-52451305-C-T		not specified • Cardiomyopathy • Dilated cardiomyopathy 1Z;Hypertrophic cardiomyopathy 13	Likely benign (Sep 11, 2018)
3-52451309-G-A		Hypertrophic cardiomyopathy 13;Dilated cardiomyopathy 1Z	Uncertain significance (Nov 03, 2022)
3-52451311-G-A		Dilated cardiomyopathy 1Z;Hypertrophic cardiomyopathy 13	Likely benign (Jun 12, 2020)
3-52451312-G-C		Hypertrophic cardiomyopathy 13;Dilated cardiomyopathy 1Z	Conflicting classifications of pathogenicity (Oct 12, 2023)
3-52451320-G-T		not specified	Benign (Jul 05, 2011)
3-52451324-G-A		Hypertrophic cardiomyopathy 13;Dilated cardiomyopathy 1Z	Likely benign (Dec 28, 2023)
3-52451325-G-T		Hypertrophic cardiomyopathy 13;Dilated cardiomyopathy 1Z	Likely benign (Feb 23, 2023)

GnomAD

Source: gnomAD

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: dbNSFP

• 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

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