TNNT1

troponin T1, slow skeletal type, the group of Troponin complex subunits

Basic information

Region (hg38): 19:55132698-55149206

Links

ENSG00000105048 ∙ NCBI:7138 ∙ OMIM:191041 ∙ HGNC:11948 ∙ Uniprot:P13805 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• nemaline myopathy 5 (Supportive), mode of inheritance: AR
• nemaline myopathy 5 (Strong), mode of inheritance: AR
• nemaline myopathy 5 (Strong), mode of inheritance: AR
• nemaline myopathy 5C, autosomal dominant (Limited), mode of inheritance: AD
• nemaline myopathy 5C, autosomal dominant (Limited), mode of inheritance: AD
• nemaline myopathy 5 (Definitive), mode of inheritance: AR
• nemaline myopathy (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Nemaline myopathy 5C, autosomal dominant; Nemaline myopathy 5A, severe infantile; Nemaline myopathy 5B, childhood-onset	AD/AR	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	Musculoskeletal	10952871; 29178646; 29931346; 31970803; 35165004; 35510366; 35833674

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TNNT1 gene.

• Nemaline_myopathy_5 (283 variants)
• not_provided (79 variants)
• Inborn_genetic_diseases (31 variants)
• not_specified (15 variants)
• Nemaline_myopathy_5B,_autosomal_recessive,_childhood-onset (6 variants)
• TNNT1-related_disorder (6 variants)
• Nemaline_myopathy_5C,_autosomal_dominant (4 variants)
• Nemaline_Myopathy,_Recessive (2 variants)
• Myopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TNNT1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003283.6. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	54	2	57
missense	3	1	114	3	1	122
nonsense	8	2				10
start loss		1				1
frameshift	9	4				13
splice donor/acceptor (+/-2bp)	2	10	2			14
Total	22	18	117	57	3

Highest pathogenic variant AF is 0.00015174306

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TNNT1	protein_coding	protein_coding	ENST00000588981	13	16561

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.02e-14	0.0172	125711	0	37	125748	0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.990	139	176	0.790	0.0000121	1800
Missense in Polyphen		54	90.956	0.5937		824
Synonymous	-0.324	66	62.7	1.05	0.00000385	486
Loss of Function	-0.0806	20	19.6	1.02	8.48e-7	262

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000120	0.000119
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.0000545	0.0000544
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000179	0.000167
Middle Eastern	0.0000545	0.0000544
South Asian	0.000362	0.000359
Other	0.00	0.00

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.
• Disease: DISEASE: Nemaline myopathy 5 (NEM5) [MIM:605355]: A form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination. Nemaline myopathy type 5 is a severe and progressive form common among Old Order Amish. Affected infants display tremors with hypotonia and mild contractures of the shoulders and hips. Proximal contractures progressively weaken and a pectus carinatum deformity develops before children die of respiratory insufficiency, usually in the second year. {ECO:0000269|PubMed:10952871}. 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: 0.209

Intolerance Scores

• loftool: 0.132
• rvis_EVS: -0.1
• rvis_percentile_EVS: 46.49

Haploinsufficiency Scores

• pHI: 0.681
• hipred: N
• hipred_score: 0.337
• ghis: 0.540

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.503

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tnnt1
• Phenotype: muscle phenotype

Gene ontology

• Biological process: skeletal muscle contraction;muscle contraction;transition between fast and slow fiber;muscle filament sliding;slow-twitch skeletal muscle fiber contraction;sarcomere organization;negative regulation of muscle contraction;cardiac muscle contraction
• Cellular component: cytosol;troponin complex
• Molecular function: calcium ion binding;protein binding;tropomyosin binding;calcium-dependent ATPase activity;troponin T binding