TNNI2
troponin I2, fast skeletal type, the group of Troponin complex subunits
Basic information
Region (hg38): 11:1838981-1841680
Previous symbols: [ "AMCD2B" ]
Links
Phenotypes
GenCC
Source:
- distal arthrogryposis type 2B1 (Strong), mode of inheritance: AD
- digitotalar dysmorphism (Supportive), mode of inheritance: AD
- Sheldon-hall syndrome (Supportive), mode of inheritance: AD
- distal arthrogryposis type 2B1 (Moderate), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Arthrogryposis, distal, type 2B1 | AD | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Craniofacial; Musculoskeletal | 12592607; 16802141 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (48 variants)
- Distal_arthrogryposis_type_2B1 (25 variants)
- Inborn_genetic_diseases (24 variants)
- not_specified (15 variants)
- TNNI2-related_disorder (7 variants)
- Arthrogryposis_multiplex_congenita (7 variants)
- Arthrogryposis_multiplex_congenita_distal (7 variants)
- Calcaneovalgus_deformity (1 variants)
- Ulnar_deviation_of_the_wrist (1 variants)
- Congenital_finger_flexion_contractures (1 variants)
- Distal_arthrogryposis (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the TNNI2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003282.4. 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 | 17 | 21 | ||||
| missense | 36 | 43 | ||||
| nonsense | 3 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 2 | |||||
| splice donor/acceptor (+/-2bp) | 3 | |||||
| Total | 3 | 7 | 44 | 18 | 1 |
Highest pathogenic variant AF is 0.0000020522361
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| TNNI2 | protein_coding | protein_coding | ENST00000381906 | 7 | 2692 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.144 | 0.840 | 125589 | 0 | 7 | 125596 | 0.0000279 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.618 | 101 | 120 | 0.841 | 0.00000846 | 1203 |
| Missense in Polyphen | 33 | 43.378 | 0.76075 | 421 | ||
| Synonymous | -3.34 | 77 | 47.7 | 1.61 | 0.00000354 | 324 |
| Loss of Function | 2.06 | 3 | 10.1 | 0.298 | 4.28e-7 | 127 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000290 | 0.0000290 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000538 | 0.0000529 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- 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: Arthrogryposis, distal, 2B (DA2B) [MIM:601680]: A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. DA2B is characterized by contractures of the hands and feet, and a distinctive face characterized by prominent nasolabial folds, small mouth and downslanting palpebral fissures. {ECO:0000269|PubMed:12592607}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- 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;Striated Muscle Contraction;Striated Muscle Contraction;Muscle contraction
(Consensus)
Recessive Scores
- pRec
- 0.182
Intolerance Scores
- loftool
- 0.128
- rvis_EVS
- -0.3
- rvis_percentile_EVS
- 32.62
Haploinsufficiency Scores
- pHI
- 0.191
- hipred
- Y
- hipred_score
- 0.525
- ghis
- 0.587
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.868
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Medium |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Tnni2
- Phenotype
- 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);
Zebrafish Information Network
- Gene name
- tnni2a.4
- Affected structure
- fast muscle cell
- Phenotype tag
- abnormal
- Phenotype quality
- disorganized
Gene ontology
- Biological process
- skeletal muscle contraction;muscle contraction;regulation of muscle contraction;muscle filament sliding;positive regulation of transcription, DNA-templated;cardiac muscle contraction
- Cellular component
- nucleus;cytosol;troponin complex
- Molecular function
- actin binding;protein binding;troponin T binding