TTC24

Chr 1

tetratricopeptide repeat domain 24

NCBI Gene: 164118 ENSG00000187862 UniProt: A2A3L6

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.96

Clinical Summary— TTC24

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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

1 unique Pathogenic / Likely Pathogenic· 88 VUS of 102 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.96LOEUF

pLI 0.000

Z-score 1.73

OE 0.63 (0.43–0.96)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.93Z-score

OE missense 0.85 (0.77–0.94)

263 obs / 309.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.63 (0.43–0.96)

0≤0.351.4

Missense OE?0.85 (0.77–0.94)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 16 / 25.4Missense obs/exp: 263 / 309.1Syn Z: 0.96

This gene — mechanism propensity

0.74top 25%

GOF

0.77top 25%

LOF

0.2678th %ile

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

GOFprediction above median

DNprediction above median

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.

ClinVar Variant Classifications

102 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS88

Likely Benign8

Benign1

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	1
Likely Pathogenic	0	0	0	0
VUS	88	0	0	88
Likely Benign	6	0	2	8
Benign	1	0	0	1
Total	95	1	2	98

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

View in ClinVar →

17 pathogenic / likely-pathogenic (of 23) ClinVar copy-number / structural variants overlap TTC24 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →