TNNC2
protein-codingtroponin C2, fast skeletal type, the group of Troponin complex subunits|EF-hand domain containing|Cilia and flagella associated
Gene summary
Troponin (Tn), a key protein complex in the regulation of striated muscle contraction, is composed of 3 subunits. The Tn-I subunit inhibits actomyosin ATPase, the Tn-T subunit binds tropomyosin and Tn-C, while the Tn-C subunit binds calcium and overcomes the inhibitory action of the troponin complex on actin filaments. The protein encoded by this gene is the Tn-C subunit. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~10.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0859335
Submitter: PanelApp Australia
Inheritance Pattern: Unknown
Disease ID:MONDO:0859335
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0859335
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0005045
Submitter: ClinGen
TNNC2 was initially curated at expert request. No convincing evidence for a causal role for TNNC2 in HCM has been reported. Although TNNC2 encodes part of the troponin complex, which has been implicated in HCM, there is no direct evidence for an association between TNNC2 and HCM. There is no convincing case control evidence for an association between TNNC2 and HCM. The mechanism of pathogenicity is unknown. In summary, there is no reported evidence to support this gene-disease association with HCM. This gene-disease pair was originally evaluated by the HCM GCEP on 04/04/2017. It was reevaluated on 04/12/2023 by the HCVD GCEP. As a result of this reevaluation, the classification did not change.
Clinical Genomic Database (CGD)
Manifestation: Musculoskeletal
Intervention: Musculoskeletal
Rationale: Early recognition of the disease may enable neonatal and early-childhood ventilatory and related support
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TNNC2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003279.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 2 | 12 | 14 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 2 | 0 | 12 | 0 | 0 | 14 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003270.1 | 6 | MANE Select | |
| Ensembl | ENSP00000361636.3 | 6 | MANE Select | |
| Ensembl | ENSP00000361638.1 | 5 | Standard | |
| Ensembl | ENSP00000718635.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Calcium signaling pathway - Homo sapiens (human)
- Disopyramide Action Pathway
- Procainamide (Antiarrhythmic) Action Pathway
- Phenytoin (Antiarrhythmic) Action Pathway
- Fosphenytoin (Antiarrhythmic) Action Pathway
Biological Process
- skeletal muscle contraction
- regulation of muscle contraction
- muscle filament sliding
Molecular Function
- actin binding
- calcium ion binding
- protein binding
- calcium-dependent protein binding
- actin filament binding
Cellular Component
- cytosol
- troponin complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000372555
- Coding exons
- 6
- Length
- 10532
- Individuals with no LoFs
- 125737
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 11
- Defined
- 125748
- p
- 0.0000437
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.20 | 71 | 106 | 0.671 | 0.00000587 | 1094 |
| Missense (PolyPhen) | 24 | 42.338 | 0.56687 | 465 | ||
| Synonymous | 1.28 | 30 | 40.4 | 0.743 | 0.00000273 | 255 |
| Loss of Function | 1.42 | 4 | 8.47 | 0.472 | 3.59e-7 | 103 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000082 | 0.000079 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
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.;
Recessive Scores
- pRec
- 0.270
Intolerance Scores
- LoFtool
- 0.351
- RVIS EVS
- -0.01
- RVIS percentile EVS
- 52.85
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0541