TTC19

Chr 17AR

tetratricopeptide repeat domain 19

Also known as: 2010204O13Rik, MC3DN2

This gene encodes a protein with a tetratricopeptide repeat (TPR) domain containing several TPRs of about 34 aa each. These repeats are found in a variety of organisms including bacteria, fungi and plants, and are involved in a variety of functions including protein-protein interactions. This protein is embedded in the inner mitochondrial membrane and is involved in the formation of the mitochondrial respiratory chain III. It has also been suggested that this protein plays a role in cytokinesis. Mutations in this gene cause mitochondrial complex III deficiency. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2012]

GeneReviewsOMIMResearchGenerating clinical summary…
LOFmechanismARLOEUF 1.121 OMIM phenotype
Clinical SummaryTTC19
🧬
Gene-Disease Validity (ClinGen)
Leigh syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
32 unique Pathogenic / Likely Pathogenic· 190 VUS of 413 total submissions
📖
GeneReview available — TTC19
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.12LOEUF
pLI 0.000
Z-score 1.16
OE 0.73 (0.481.12)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
0.08Z-score
OE missense 0.98 (0.871.11)
176 obs / 179.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.73 (0.481.12)
00.351.4
Missense OE?0.98 (0.871.11)
00.61.4
Synonymous OE?1.19
01.21.6
LoF obs/exp: 15 / 20.7Missense obs/exp: 176 / 179.1Syn Z: -1.21
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveTTC19-related mitochondrial complex III deficiencyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6552th %ile
GOF
0.6443th %ile
LOF
0.2871th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

413 submitted variants in ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic13
VUS190
Likely Benign114
Benign38
Conflicting24
19
Pathogenic
13
Likely Pathogenic
190
VUS
114
Likely Benign
38
Benign
24
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
16
0
3
0
19
Likely Pathogenic
12
1
0
0
13
VUS
6
115
65
4
190
Likely Benign
0
8
62
44
114
Benign
1
0
35
2
38
Conflicting
24
Total3512416550398

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

25 pathogenic / likely-pathogenic (of 46) ClinVar copy-number / structural variants overlap TTC19 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

TTC19 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →