Disease and Mutation LabMechanism before phenotype
Genotype → biophysics → phenotype
Change the lesion. Follow what breaks.
Compare a curated cardiac variant with the reference state, add a mechanism-based intervention overlay, and trace the consequences from calcium handling to ventricular output.
thin-filament calcium sensitization
TNNT2 p.Arg92Gln · R92Q
autosomal dominantHypertrophic cardiomyopathy
02Calcium and force through one cycle
referenceselected state
The thin filament activates at lower cytosolic Ca²⁺, represented by a left-shifted force–calcium relation.
More force persists while calcium falls, increasing residual diastolic tension and energetic demand.
A smaller, stiffer chamber can remain hyperdynamic while filling pressure rises.
The molecule itself
Look at what the lesion actually changes.
Every trace above is driven by a parameter. This is the protein those parameters stand for, traced from the mmCIF this deployment has cached — the same bytes the download gives you.
6KN7Cardiac thin filament · calcium-free, Arg92 resolved
Loading structure from the local cache…
troponin Trest of the complex
Intervention reasoning
See the tradeoff, not just the endpoint.
The untreated selected state remains visible while the overlay changes only its encoded target mechanisms. Reference physiology is retained as a separate anchor.
Ventricular consequencePressure-volume comparison
referenceuntreated variantoverlay
Overlay EF73%fittedStroke volume80 mLfittedCardiac output6.46 L/minfitted
Evidence map
Separate observation from translation.
The direction of each primary molecular effect is literature-grounded. Numeric parameter sizes and organ-scale consequences are teaching assumptions.
Supported direction
The thin filament activates at lower cytosolic Ca²⁺, represented by a left-shifted force–calcium relation.
Model translation
Open evidence source ↗A smaller, stiffer chamber can remain hyperdynamic while filling pressure rises.
Supported direction
Less cardiac myosin-binding protein C shifts myosin heads out of the energy-sparing super-relaxed state.
Model translation
Open evidence source ↗Hypercontractility and impaired relaxation in a relatively small, stiff chamber.
Supported direction
The thin filament needs more Ca²⁺ for the same activation, represented by a right-shifted force–calcium relation.
Model translation
Open evidence source ↗Lower elastance with compensatory dilation gives a wider chamber and reduced ejection fraction.
Supported direction
Destabilized RyR2 gating permits spontaneous sarcoplasmic-reticulum Ca²⁺ release during diastole.
Model translation
Open evidence source ↗Pump output stays near normal while electrical instability rises sharply with adrenergic drive.
For example, calcium sensitization, desensitization, or stress-dependent RyR2 leak.
Compliance, chamber filling, reserve, and energetic multipliers are selected for interpretable teaching behavior.
Calcium occupancy, force, pressure-volume loops, EF, and output emerge from the reduced model.
Penetrance, fibrosis, LVOT anatomy, ECG behavior, sudden-death risk, and treatment response remain outside scope.
The simulator isolates selected mechanisms and then propagates them through a reduced cardiac model. It does not estimate penetrance, clinical severity, sudden-death risk, treatment response, or prognosis for a person carrying a variant.