TRDN

triadin

Basic information

Region (hg38): 6:123216338-123637093

Links

ENSG00000186439 ∙ NCBI:10345 ∙ OMIM:603283 ∙ HGNC:12261 ∙ Uniprot:Q13061 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• catecholaminergic polymorphic ventricular tachycardia 5 (Strong), mode of inheritance: AR
• catecholaminergic polymorphic ventricular tachycardia (Supportive), mode of inheritance: AD
• catecholaminergic polymorphic ventricular tachycardia 5 (Strong), mode of inheritance: AR
• catecholaminergic polymorphic ventricular tachycardia 5 (Definitive), mode of inheritance: AR
• familial long QT syndrome (Strong), mode of inheritance: AR
• long QT syndrome (Strong), mode of inheritance: AR
• catecholaminergic polymorphic ventricular tachycardia (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiac arrhythmia syndrome with or without skeletal muscle weakness	AR	Cardiovascular	Individuals may present with severe cardiac manifestations, including arrhythmias, syncope, and sudden death, and surveillance, preventive measures (eg, including avoidance of dangerous or excacerbating factors), and treatment (eg, including interventions such as medical treatment with beta-blockers or ICD placement) may allow early and beneficial management, which may decrease morbidity and mortality	Cardiovascular; Musculoskeletal; Neurologic	22422768; 25922419; 30649896

ClinVar

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

• Catecholaminergic polymorphic ventricular tachycardia 1 (777 variants)
• Cardiovascular phenotype (325 variants)
• not provided (263 variants)
• not specified (78 variants)
• Catecholaminergic polymorphic ventricular tachycardia 5 (52 variants)
• Catecholaminergic polymorphic ventricular tachycardia 1;Catecholaminergic polymorphic ventricular tachycardia 5 (29 variants)
• Catecholaminergic polymorphic ventricular tachycardia 5;Catecholaminergic polymorphic ventricular tachycardia 1 (29 variants)
• Catecholaminergic polymorphic ventricular tachycardia (20 variants)
• Inborn genetic diseases (13 variants)
• TRDN-related condition (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRDN 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			5	118		123
missense			362	20	6	388
nonsense	6	3	15			24
start loss	1					1
frameshift	11	7	13	1	1	33
inframe indel			10		1	11
splice donor/acceptor (+/-2bp)	3	8	33			44
splice region			48	69	6	123
non coding	1	1	10	218	102	332
Total	22	19	448	357	110

Highest pathogenic variant AF is 0.000197

Variants in TRDN

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

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

Position	Type	Phenotype	Significance	ClinVar
6-123217141-A-ATG		Catecholaminergic polymorphic ventricular tachycardia	Uncertain significance (Jun 14, 2016)
6-123218381-G-A			Benign (Jul 21, 2018)
6-123218464-C-T			Benign (Jun 14, 2018)
6-123218479-A-T			Likely benign (Jun 26, 2018)
6-123218539-C-T			Benign (Jun 14, 2018)
6-123218540-T-C			Benign (Jun 14, 2018)
6-123218582-A-C			Likely benign (Jan 26, 2017)
6-123218586-G-A			Likely benign (May 03, 2018)
6-123218602-T-C		Cardiovascular phenotype	Likely benign (Nov 26, 2019)
6-123218603-A-G		Cardiovascular phenotype	Uncertain significance (Oct 31, 2023)
6-123218604-C-A		Cardiovascular phenotype • Catecholaminergic polymorphic ventricular tachycardia 1	Uncertain significance (Jun 02, 2023)
6-123218606-G-A		Catecholaminergic polymorphic ventricular tachycardia 1	Uncertain significance (Aug 18, 2020)
6-123218606-G-C		Catecholaminergic polymorphic ventricular tachycardia 1	Uncertain significance (Apr 28, 2022)
6-123218608-C-A		Cardiovascular phenotype	Uncertain significance (Jan 22, 2023)
6-123218609-C-T		Catecholaminergic polymorphic ventricular tachycardia 1 • Cardiovascular phenotype	Uncertain significance (May 27, 2023)
6-123218611-T-C		Catecholaminergic polymorphic ventricular tachycardia 1 • Cardiovascular phenotype	Uncertain significance (Nov 01, 2023)
6-123218612-G-A		Cardiovascular phenotype • Catecholaminergic polymorphic ventricular tachycardia 1;Catecholaminergic polymorphic ventricular tachycardia 5 • Catecholaminergic polymorphic ventricular tachycardia 1	Uncertain significance (Mar 13, 2023)
6-123218615-G-A		Cardiovascular phenotype • Catecholaminergic polymorphic ventricular tachycardia 1;Catecholaminergic polymorphic ventricular tachycardia 5 • Catecholaminergic polymorphic ventricular tachycardia 1	Uncertain significance (Dec 15, 2021)
6-123218622-T-C		Catecholaminergic polymorphic ventricular tachycardia 1	Likely benign (Nov 21, 2022)
6-123218624-C-T		Catecholaminergic polymorphic ventricular tachycardia 1	Uncertain significance (Sep 02, 2021)
6-123218626-G-A		Catecholaminergic polymorphic ventricular tachycardia 1	Uncertain significance (Nov 01, 2021)
6-123218627-G-C		Cardiovascular phenotype • Catecholaminergic polymorphic ventricular tachycardia 1	Uncertain significance (Jul 10, 2022)
6-123218631-A-G		Catecholaminergic polymorphic ventricular tachycardia 1	Likely benign (Feb 20, 2022)
6-123218637-T-G		Cardiovascular phenotype	Uncertain significance (Nov 04, 2022)
6-123218640-ACC-A		Catecholaminergic polymorphic ventricular tachycardia 1	Uncertain significance (Jul 26, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRDN	protein_coding	protein_coding	ENST00000398178	41	420756

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.36e-22	0.0920	124508	2	127	124637	0.000518

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0770	294	290	1.01	0.0000136	4687
Missense in Polyphen		60	59.054	1.016		1102
Synonymous	0.0815	93	94.0	0.989	0.00000487	1180
Loss of Function	1.46	39	50.1	0.778	0.00000242	826

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00149	0.00148
Ashkenazi Jewish	0.00	0.00
East Asian	0.000341	0.000334
Finnish	0.00	0.00
European (Non-Finnish)	0.000551	0.000531
Middle Eastern	0.000341	0.000334
South Asian	0.00134	0.00118
Other	0.000356	0.000330

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Contributes to the regulation of lumenal Ca2+ release via the sarcoplasmic reticulum calcium release channels RYR1 and RYR2, a key step in triggering skeletal and heart muscle contraction. Required for normal organization of the triad junction, where T-tubules and the sarcoplasmic reticulum terminal cisternae are in close contact (By similarity). Required for normal skeletal muscle strength. Plays a role in excitation- contraction coupling in the heart and in regulating the rate of heart beats. {ECO:0000250|UniProtKB:E9Q9K5, ECO:0000269|PubMed:22422768}.
• Disease: DISEASE: Ventricular tachycardia, catecholaminergic polymorphic, 5, with or without muscle weakness (CPVT5) [MIM:615441]: An arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death. Patients present with recurrent syncope, or sudden death after physical activity or emotional stress. Some patients have muscle weakness. CPVT5 inheritance is autosomal recessive. {ECO:0000269|PubMed:22422768}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Stimuli-sensing channels;Ion channel transport;Ion homeostasis;Transport of small molecules;Cardiac conduction;Muscle contraction (Consensus)

Recessive Scores

• pRec: 0.159

Intolerance Scores

• loftool: 0.861
• rvis_EVS: 1.98
• rvis_percentile_EVS: 97.61

Haploinsufficiency Scores

• pHI: 0.182
• hipred: N
• hipred_score: 0.203
• ghis: 0.396

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.275

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Trdn
• Phenotype: muscle phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: cellular calcium ion homeostasis;muscle contraction;response to bacterium;regulation of cell communication by electrical coupling;regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum;release of sequestered calcium ion into cytosol by sarcoplasmic reticulum;cytoplasmic microtubule organization;ion transmembrane transport;regulation of release of sequestered calcium ion into cytosol;heart contraction;negative regulation of ryanodine-sensitive calcium-release channel activity;positive regulation of ryanodine-sensitive calcium-release channel activity;regulation of cardiac muscle cell membrane potential;endoplasmic reticulum membrane organization;positive regulation of cell communication by electrical coupling involved in cardiac conduction;regulation of cardiac conduction
• Cellular component: endoplasmic reticulum;cytosol;plasma membrane;junctional sarcoplasmic reticulum membrane;integral component of membrane;sarcoplasmic reticulum;junctional membrane complex;sarcoplasmic reticulum membrane;sarcoplasmic reticulum lumen
• Molecular function: signaling receptor binding;protein binding;protein binding, bridging;ion channel binding