TNNI3K

TNNI3 interacting kinase, the group of Ankyrin repeat domain containing

Basic information

Region (hg38): 1:74235386-74544428

Links

ENSG00000116783 ∙ NCBI:51086 ∙ OMIM:613932 ∙ HGNC:19661 ∙ Uniprot:Q59H18 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• atrial conduction disease (Strong), mode of inheritance: AD
• atrial conduction disease (Limited), mode of inheritance: AD
• atrial conduction disease (Supportive), mode of inheritance: AD
• atrial conduction disease (Strong), mode of inheritance: AD
• dilated cardiomyopathy (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiac conduction disease with or without dilated cardiomyopathy	AD	Cardiovascular	Individuals have been described with arrhythmia and cardiomyopathy, and awareness may allow early medical/surgical management (eg, medical management and catheter-based ablation of cardiac foci has been described as beneficial)	Cardiovascular	24925317; 25791106; 30010057

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TNNI3K gene.

• not provided (749 variants)
• Atrial conduction disease (45 variants)
• Inborn genetic diseases (39 variants)
• TNNI3K-related condition (6 variants)
• not specified (5 variants)
• Primary dilated cardiomyopathy (3 variants)
• Arrhythmogenic right ventricular dysplasia 2 (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TNNI3K 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			7	82	8	97
missense		4	360	13	8	385
nonsense			26	2		28
start loss			1			1
frameshift			21		1	22
inframe indel			5			5
splice donor/acceptor (+/-2bp)			24	1		25
splice region			31	23	9	63
non coding			6	82	52	140
Total	0	4	450	180	69

Variants in TNNI3K

This is a list of pathogenic ClinVar variants found in the TNNI3K region.

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

Position	Type	Phenotype	Significance	ClinVar
1-74235452-A-G			Uncertain significance (Nov 01, 2023)
1-74235453-T-A			Uncertain significance (May 05, 2022)
1-74235456-GAAATTAT-G			Uncertain significance (Jun 08, 2022)
1-74235470-A-G		Atrial conduction disease	Uncertain significance (Jan 05, 2024)
1-74235472-A-G			Likely benign (Aug 16, 2023)
1-74235473-C-T			Uncertain significance (May 18, 2022)
1-74235474-C-A			Uncertain significance (Sep 03, 2023)
1-74235478-C-A			Likely benign (Dec 26, 2023)
1-74235479-C-A			Uncertain significance (Jan 12, 2024)
1-74235485-TGTACTG-T			Uncertain significance (Oct 13, 2023)
1-74235486-G-A			Uncertain significance (Jan 19, 2023)
1-74235488-A-G			Uncertain significance (Dec 04, 2023)
1-74235493-T-C			Uncertain significance (Sep 02, 2021)
1-74235611-T-A			Benign (Apr 04, 2019)
1-74235967-A-T			Benign (Mar 01, 2019)
1-74236083-A-G			Likely benign (Nov 26, 2022)
1-74236087-G-C			Likely benign (Jan 15, 2024)
1-74236087-G-T			Likely benign (Jun 05, 2023)
1-74236090-C-T			Likely benign (Aug 04, 2023)
1-74236093-C-CT			Likely benign (Apr 24, 2023)
1-74236102-A-G			Uncertain significance (Sep 13, 2023)
1-74236103-T-A			Uncertain significance (Jul 08, 2022)
1-74236104-G-A			Uncertain significance (Jul 28, 2023)
1-74236118-A-T			Uncertain significance (Mar 07, 2023)
1-74236119-GTCAGTGAA-G			Uncertain significance (Sep 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TNNI3K	protein_coding	protein_coding	ENST00000370891	27	346166

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.07e-48	2.37e-9	125048	5	695	125748	0.00279

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.553	532	497	1.07	0.0000251	6093
Missense in Polyphen		217	219.02	0.99078		2661
Synonymous	0.0628	178	179	0.994	0.00000896	1769
Loss of Function	-1.15	67	57.6	1.16	0.00000299	694

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0105	0.0104
Ashkenazi Jewish	0.000102	0.0000992
East Asian	0.00237	0.00234
Finnish	0.0000472	0.0000462
European (Non-Finnish)	0.00171	0.00169
Middle Eastern	0.00237	0.00234
South Asian	0.00487	0.00475
Other	0.00296	0.00277

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play a role in cardiac physiology. {ECO:0000303|PubMed:12721663}.
• Disease: DISEASE: Cardiac conduction disease with or without dilated cardiomyopathy (CCDD) [MIM:616117]: A cardiac disorder characterized by atrial tachyarrhythmia and conduction system disease. Some patients have dilated cardiomyopathy. {ECO:0000269|PubMed:24925317}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.108

Intolerance Scores

• loftool: 0.547
• rvis_EVS: -0.35
• rvis_percentile_EVS: 29.59

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.146
• ghis: 0.502

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.822

Mouse Genome Informatics

• Gene name: Tnni3k
• Phenotype: muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; 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)

Gene ontology

• Biological process: regulation of heart rate;protein phosphorylation;regulation of cardiac muscle contraction;bundle of His cell to Purkinje myocyte communication;regulation of cardiac conduction
• Cellular component: nucleus;cytoplasm
• Molecular function: protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding;protein C-terminus binding;troponin I binding;metal ion binding