TNNI2

troponin I2, fast skeletal type, the group of Troponin complex subunits

Basic information

Region (hg38): 11:1838980-1841680

Previous symbols: [ "AMCD2B" ]

Links

ENSG00000130598 ∙ NCBI:7136 ∙ OMIM:191043 ∙ HGNC:11946 ∙ Uniprot:P48788 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the TNNI2 gene.

• Distal arthrogryposis type 2B1 (2 variants)
• not provided (2 variants)
• Congenital finger flexion contractures;Distal arthrogryposis;Ulnar deviation of the wrist;Calcaneovalgus deformity (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.

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			3	9	2	14
missense	1	4	23			28
nonsense	1	2				3
start loss			1			1
frameshift			1			1
inframe indel		3				3
splice donor/acceptor (+/-2bp)		1	2			3
splice region				4	1	5
non coding			7	13	6	26
Total	2	10	37	22	8

Variants in TNNI2

This is a list of pathogenic ClinVar variants found in the TNNI2 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-1838988-C-T		Distal arthrogryposis type 2B1	Uncertain significance (Jan 13, 2018)
11-1839006-G-A		Distal arthrogryposis type 2B1 • Arthrogryposis multiplex congenita	Uncertain significance (Jan 12, 2018)
11-1839047-C-T		not specified	Likely benign (Sep 26, 2017)
11-1839052-C-T		not specified	Likely benign (Sep 07, 2017)
11-1839074-G-A			Benign (Nov 19, 2019)
11-1839194-G-C			Benign (Nov 19, 2019)
11-1839408-C-T			Likely benign (Apr 21, 2019)
11-1839699-G-A			Uncertain significance (Dec 01, 2016)
11-1839720-G-A		not specified	Likely benign (Jul 31, 2017)
11-1839732-A-G		not specified	Likely benign (Aug 17, 2018)
11-1839848-G-C		Distal arthrogryposis type 2B1	Uncertain significance (May 23, 2022)
11-1839863-G-C		not specified	Likely benign (Sep 29, 2017)
11-1839876-C-G			not provided (-)
11-1839995-C-A			Benign (Jun 26, 2018)
11-1840381-CCCCCTGT-C			Likely benign (Jun 14, 2018)
11-1840420-C-T			Likely benign (Jan 30, 2020)
11-1840423-G-A		TNNI2-related disorder	Likely benign (Sep 01, 2022)
11-1840428-G-A		Inborn genetic diseases	Uncertain significance (Mar 14, 2024)
11-1840441-G-C		Arthrogryposis multiplex congenita • not specified • Arthrogryposis multiplex congenita distal	Conflicting classifications of pathogenicity (Dec 16, 2019)
11-1840461-G-C		not specified	Likely benign (Jan 30, 2018)
11-1840524-G-A		not specified	Likely benign (Dec 05, 2017)
11-1840530-T-C		not specified • Arthrogryposis multiplex congenita • Distal arthrogryposis type 2B1	Benign/Likely benign (Jul 14, 2021)
11-1840531-G-A		Arthrogryposis multiplex congenita • Arthrogryposis multiplex congenita distal • Inborn genetic diseases	Conflicting classifications of pathogenicity (Sep 07, 2022)
11-1840553-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Nov 07, 2022)
11-1840572-G-A			Conflicting classifications of pathogenicity (Dec 14, 2018)

GnomAD

Source: gnomAD

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: 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: 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