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CACNA1C Variant Long QT Risk Model Calculator

  • QTc (ms)
  • Prior cardiac arrest (resuscitated)?
     
  • Unexplained syncope?
     
  • Family history of sudden cardiac death (first-degree relative <50 years)?
     
  • Variant functional evidence
  • Age (years)
  • Sex
     
  • CACNA1C Variant Long QT Risk Model — Explanation and Clinical Context
    This tool estimates relative arrhythmic risk in carriers of CACNA1C variants by combining well-recognized predictors from long QT syndrome (LQTS) literature — especially QTc duration and history of syncope or prior cardiac arrest — with gene-specific considerations such as experimentally demonstrated gain-of-function in CACNA1C. QTc elevation, especially QTc >= 500 ms, and history of unexplained syncope or prior resuscitated cardiac arrest are consistently associated with higher arrhythmic risk in LQTS cohorts and are therefore given major weight in this estimator. Functional evidence that a CACNA1C variant produces a gain-of-function (increased L-type calcium current or impaired inactivation) increases biological plausibility for arrhythmia and is therefore given additional weight. Age modifies penetrance; younger carriers often express phenotype earlier and are given a small additional weight.

    How to interpret the output: The numeric score is a relative index — higher scores indicate greater relative risk. The mapped approximate annual risk bands are illustrative and intentionally broad; they are adapted from general LQTS risk literature rather than from a CACNA1C-specific prospective model. This calculator should be used only as a supplementary aid; definitive clinical decisions must incorporate full phenotyping, specialist review, and guideline recommendations.

    Reference:
    GeneReviews: Napolitano C, et al. "CACNA1C-Related Disorders" (GeneReviews, NCBI Bookshelf). This resource summarizes CACNA1C roles in LQT8/Timothy syndrome and variable expressivity.
    Fukuyama M, et al. "Long QT syndrome type 8: novel CACNA1C mutations causing QT prolongation and variant phenotypes." Europace. 2014 — description of CACNA1C variants and clinical heterogeneity.
    Mellor GJ, et al. "Pathogenic variants in CACNA1C-encoded Cav1.2..." (manuscript summarizing ECG features and risk). 2019 — highlights arrhythmic risk despite variable QT prolongation.
    AHA/ESC LQTS literature (e.g., Schwartz/Mazzanti/AHA reviews) describing QTc >= 500 ms and prior syncope/resuscitated arrest as strong risk predictors in LQTS cohorts.