TTC14

Chr 3

tetratricopeptide repeat domain 14

Also known as: DRDL5813, PRO19630

NCBI Gene: 151613 ENSG00000163728 UniProt: Q96N46

Predicted to enable nucleic acid binding activity. [provided by Alliance of Genome Resources, Jul 2025]

Research

Predicted to enable nucleic acid binding activity. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.83

Clinical Summary— TTC14

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

25 unique Pathogenic / Likely Pathogenic· 168 VUS of 333 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.83LOEUF

pLI 0.000

Z-score 2.33

OE 0.57 (0.40–0.83)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.30Z-score

OE missense 0.96 (0.88–1.04)

371 obs / 387.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.57 (0.40–0.83)

0≤0.351.4

Missense OE?0.96 (0.88–1.04)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 20 / 34.8Missense obs/exp: 371 / 387.5Syn Z: -0.14

This gene — mechanism propensity

0.6649th %ile

GOF

0.5367th %ile

LOF

0.4627th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

LOF100% of P/LP variants are LoF

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

333 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15

Likely Pathogenic10

VUS168

Likely Benign90

Benign15

Conflicting15

Pathogenic

Likely Pathogenic

168

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	15	0	0	0	15
Likely Pathogenic	10	0	0	0	10
VUS	1	139	27	1	168
Likely Benign	1	8	34	47	90
Benign	0	1	10	4	15
Conflicting	—				15
Total	27	148	71	52	313

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

View in ClinVar →

29 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap TTC14 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →