TTC19

tetratricopeptide repeat domain 19, the group of Mitochondrial respiratory chain complex assembly factors|Tetratricopeptide repeat domain containing

Basic information

Region (hg38): 17:15999784-16045015

Links

ENSG00000011295 ∙ NCBI:54902 ∙ OMIM:613814 ∙ HGNC:26006 ∙ Uniprot:Q6DKK2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex III deficiency nuclear type 1 (Definitive), mode of inheritance: AR
• mitochondrial complex III deficiency nuclear type 2 (Strong), mode of inheritance: AR
• mitochondrial complex III deficiency nuclear type 2 (Strong), mode of inheritance: AR
• mitochondrial complex III deficiency (Supportive), mode of inheritance: AR
• mitochondrial complex III deficiency nuclear type 2 (Moderate), mode of inheritance: AR
• Leigh syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex III deficiency, nuclear type 2	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	Biochemical; Musculoskeletal; Neurologic	21278747; 23532514; 24368687; 24397319
Individuals may suffer acute episodes of metabolic crisis; Treatment with "Mitochondrial cocktail" type therapy may be beneficial

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TTC19 gene.

• not provided (6 variants)
• Mitochondrial complex III deficiency nuclear type 2 (4 variants)
• Inborn genetic diseases (1 variants)
• Mitochondrial disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TTC19 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	33	1	35
missense			67	3		70
nonsense	6	1	3			10
start loss						0
frameshift	2	1			1	4
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	7				8
splice region			6	4		10
non coding			40	42	31	113
Total	9	9	112	78	33

Highest pathogenic variant AF is 0.0000394

Variants in TTC19

This is a list of pathogenic ClinVar variants found in the TTC19 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-15999787-G-A		Inborn genetic diseases	Uncertain significance (Nov 30, 2021)
17-15999795-G-T		Inborn genetic diseases	Uncertain significance (Aug 19, 2021)
17-15999798-G-T		Inborn genetic diseases	Uncertain significance (Jan 31, 2024)
17-15999799-G-C		Inborn genetic diseases	Uncertain significance (Mar 22, 2023)
17-15999799-G-T		TTC19-related disorder	Likely benign (Jan 02, 2020)
17-15999805-A-G		not specified • TTC19-related disorder	Likely benign (Aug 07, 2013)
17-15999807-G-T			Pathogenic (Jun 25, 2013)
17-15999814-T-A		Inborn genetic diseases	Uncertain significance (May 24, 2024)
17-15999831-A-G		Inborn genetic diseases	Uncertain significance (Jun 07, 2023)
17-15999834-G-A		not specified • Mitochondrial complex III deficiency nuclear type 2	Benign (Jan 12, 2018)
17-15999848-C-G			Uncertain significance (Jun 21, 2019)
17-15999848-C-T		not specified • Mitochondrial complex III deficiency nuclear type 2	Conflicting classifications of pathogenicity (Apr 27, 2017)
17-15999849-A-G		Inborn genetic diseases • Mitochondrial complex III deficiency nuclear type 2	Conflicting classifications of pathogenicity (May 04, 2022)
17-15999852-T-G			Uncertain significance (Aug 15, 2022)
17-15999855-C-T		Mitochondrial complex III deficiency nuclear type 2	Conflicting classifications of pathogenicity (Mar 26, 2024)
17-15999857-G-T			Likely benign (Apr 24, 2022)
17-15999865-G-A		Inborn genetic diseases	Uncertain significance (Jun 26, 2023)
17-15999871-G-C		not specified	Likely benign (Dec 17, 2013)
17-15999873-C-T		Mitochondrial complex III deficiency nuclear type 2	Conflicting classifications of pathogenicity (Dec 31, 2019)
17-15999875-G-C		not specified	Benign/Likely benign (Nov 19, 2023)
17-15999886-T-G			Uncertain significance (Dec 07, 2023)
17-15999897-G-A		Inborn genetic diseases	Uncertain significance (Jul 17, 2023)
17-15999915-G-A			Uncertain significance (Dec 06, 2023)
17-15999919-G-A		Inborn genetic diseases	Uncertain significance (Aug 15, 2023)
17-15999935-C-G			Likely benign (Mar 31, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TTC19	protein_coding	protein_coding	ENST00000261647	10	45636

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.38e-8	0.594	125621	0	127	125748	0.000505

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0827	176	179	0.983	0.00000880	2434
Missense in Polyphen		51	56.365	0.90482		761
Synonymous	-1.21	79	66.4	1.19	0.00000331	745
Loss of Function	1.16	15	20.7	0.725	9.77e-7	251

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000735	0.000735
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000381	0.000381
Finnish	0.000231	0.000231
European (Non-Finnish)	0.000766	0.000765
Middle Eastern	0.000381	0.000381
South Asian	0.000131	0.000131
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for the preservation of the structural and functional integrity of mitochondrial respiratory complex III by allowing the physiological turnover of the Rieske protein UQCRFS1 (PubMed:21278747, PubMed:28673544). Involved in the clearance of UQCRFS1 N-terminal fragments, which are produced upon incorporation of UQCRFS1 into the complex III and whose presence is detrimental for its catalytic activity (PubMed:28673544). {ECO:0000269|PubMed:21278747, ECO:0000269|PubMed:28673544}.
• Disease: DISEASE: Mitochondrial complex III deficiency, nuclear 2 (MC3DN2) [MIM:615157]: A disorder of the mitochondrial respiratory chain resulting in a highly variable phenotype depending on which tissues are affected. Clinical features include mitochondrial encephalopathy, psychomotor retardation, ataxia, severe failure to thrive, liver dysfunction, renal tubulopathy, muscle weakness and exercise intolerance. {ECO:0000269|PubMed:21278747}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0786

Haploinsufficiency Scores

• pHI: 0.255
• hipred: N
• hipred_score: 0.144
• ghis: 0.413

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0761

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ttc19

Gene ontology

• Biological process: mitotic cytokinesis;mitochondrial respiratory chain complex III assembly;oxidation-reduction process
• Cellular component: mitochondrion;mitochondrial inner membrane;centrosome;midbody;respirasome
• Molecular function: protein binding