Timothy syndrome: genes and variants
Timothy syndrome is linked to 1 analyzed protein (CACNA1C). 4 DNA variants are known to cause it; 5 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Timothy syndrome
CACNA1C: Voltage-dependent L-type calcium channel subunit alpha-1C
Its opening provides a major source of depolarization-triggered calcium entry in cardiomyocytes, smooth muscle, and neurons, coupling electrical activity to contraction and signaling. Pathogenic variants can cause Timothy syndrome, Brugada or long-QT phenotypes, and several neurodevelopmental disorders.
4 disease-causing and 5 uncertain variants in CACNA1C are linked to Timothy syndrome.
Known disease-causing variants in Timothy syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| CACNA1C G406R | 406 | I | Disease-causing (★★) |
| CACNA1C I1186T | 1186 | III | Disease-causing (★★) |
| CACNA1C V1187A | 1187 | III | Disease-causing (★★) |
| CACNA1C V1411L | 1411 | IV | Disease-causing |
Same protein, different disease
- Long QT syndrome is also caused by CACNA1C variants; they fall mostly in different places as the Timothy syndrome variants (12 disease-causing).
Diseases related to Timothy syndrome
- Long QT syndrome, also linked to CACNA1C
- Cardiac arrhythmia, also linked to CACNA1C
- Brugada syndrome, also linked to CACNA1C
- Epilepsy, also linked to CACNA1C
- Diabetes mellitus, also linked to CACNA1C
- Myocardial infarction, also linked to CACNA1C
- Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures, also linked to CACNA1C
Frequently asked questions
Which genes are linked to Timothy syndrome?
In CATVariant, Timothy syndrome is linked to 1 analyzed protein: CACNA1C (Voltage-dependent L-type calcium channel subunit alpha-1C).
How many genetic variants are linked to Timothy syndrome?
10 variants: 4 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 5 are of uncertain significance or have conflicting reports.
Which uncertain variants in Timothy syndrome look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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