TNNT3

troponin T3, fast skeletal type, the group of Troponin complex subunits

Basic information

Region (hg38): 11:1919702-1938706

Links

ENSG00000130595 ∙ NCBI:7140 ∙ OMIM:600692 ∙ HGNC:11950 ∙ Uniprot:P45378 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• digitotalar dysmorphism (Supportive), mode of inheritance: AD
• Sheldon-hall syndrome (Supportive), mode of inheritance: AD
• arthrogryposis, distal, type 2B2 (Moderate), mode of inheritance: AD
• nemaline myopathy (Moderate), mode of inheritance: AR
• distal arthrogryposis type 2B1 (Strong), mode of inheritance: AD
• nemaline myopathy (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Arthyrgryposis, distal, type 2B2	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	12865991

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TNNT3 gene.

• not provided (181 variants)
• not specified (18 variants)
• Distal arthrogryposis type 2B1 (18 variants)
• Arthrogryposis multiplex congenita (17 variants)
• Arthrogryposis multiplex congenita distal (17 variants)
• Arthrogryposis, distal, type 2B2 (13 variants)
• Inborn genetic diseases (9 variants)
• TNNT3-related condition (2 variants)
• Arthyrgryposis, distal, type 2B (2 variants)
• Microcephaly;Isolated Pierre-Robin syndrome;Skeletal dysplasia;Distal arthrogryposis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TNNT3 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			1	16	3	20
missense		3	52	1	2	58
nonsense			1			1
start loss						0
frameshift						0
inframe indel			2	1		3
splice donor/acceptor (+/-2bp)	1		4			5
splice region			6	5	1	12
non coding			5	41	44	90
Total	1	3	65	59	49

Variants in TNNT3

This is a list of pathogenic ClinVar variants found in the TNNT3 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-1919759-G-T		Distal arthrogryposis type 2B1 • Arthrogryposis multiplex congenita distal	Uncertain significance (Jan 12, 2018)
11-1922375-G-A			not provided (Mar 18, 2012)
11-1922478-C-A			not provided (Mar 18, 2012)
11-1922639-C-T			Benign (Oct 28, 2019)
11-1922820-C-CCT			Benign (Apr 28, 2020)
11-1922882-A-T			Benign (Dec 22, 2023)
11-1922885-A-T			Uncertain significance (Sep 09, 2023)
11-1922887-G-A			Uncertain significance (Jun 17, 2021)
11-1922972-A-G		Arthrogryposis, distal, type 2B2	Benign (Jul 14, 2021)
11-1923040-C-A			Likely benign (Sep 19, 2023)
11-1923047-G-T			Uncertain significance (Sep 27, 2022)
11-1923076-C-G			Likely benign (Jul 06, 2022)
11-1923406-A-T		Arthrogryposis, distal, type 2B2	Benign (Jul 14, 2021)
11-1923544-TC-AA			Uncertain significance (Sep 09, 2023)
11-1923552-C-T			Uncertain significance (Oct 19, 2023)
11-1923557-C-A			Uncertain significance (Jun 17, 2021)
11-1923560-T-C		Arthrogryposis, distal, type 2B2	Uncertain significance (-)
11-1923562-C-A			Uncertain significance (Apr 24, 2022)
11-1923562-C-T			Likely benign (Dec 09, 2023)
11-1923562-CGAA-C			Likely benign (Oct 04, 2023)
11-1923564-A-G			Uncertain significance (Sep 09, 2023)
11-1923589-C-T			Likely benign (Nov 22, 2023)
11-1923590-C-T			Likely benign (Oct 04, 2023)
11-1923591-G-A			Likely benign (Mar 23, 2023)
11-1923624-C-A			Likely benign (Nov 14, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TNNT3	protein_coding	protein_coding	ENST00000278317	15	19145

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.08e-7	0.891	125724	0	24	125748	0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.463	130	146	0.892	0.00000999	1723
Missense in Polyphen		47	54.678	0.85958		658
Synonymous	-0.644	57	51.1	1.11	0.00000356	412
Loss of Function	1.65	14	22.4	0.624	0.00000121	279

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000400	0.000397
Ashkenazi Jewish	0.000100	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000709	0.0000703
Middle Eastern	0.00	0.00
South Asian	0.000198	0.000196
Other	0.000169	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Troponin T is the tropomyosin-binding subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.
• 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: 0.157

Intolerance Scores

• loftool: 0.214
• rvis_EVS: -0.41
• rvis_percentile_EVS: 26.23

Haploinsufficiency Scores

• pHI: 0.307
• hipred: Y
• hipred_score: 0.726
• ghis: 0.583

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.660

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tnnt3
• Phenotype: liver/biliary system 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); limbs/digits/tail phenotype; renal/urinary system phenotype; skeleton phenotype; growth/size/body region phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: tnnt3b
• Affected structure: fast muscle cell
• Phenotype tag: abnormal
• Phenotype quality: disorganized

Gene ontology

• Biological process: skeletal muscle contraction;muscle contraction;regulation of striated muscle contraction;muscle filament sliding;regulation of ATPase activity;sarcomere organization;cardiac muscle contraction
• Cellular component: cytosol;troponin complex
• Molecular function: actin binding;calcium ion binding;protein binding;tropomyosin binding;troponin C binding;calcium-dependent ATPase activity;troponin I binding;calcium-dependent protein binding