We complement variant classification with quantitative penetrance estimates: a calibrated probability of disease for each variant, built from published carriers, high-throughput functional data, protein structure and Bayesian modeling.
Observed proportions of published SCN5A heterozygotes diagnosed with Brugada syndrome: 1/13 (8%), 5/12 (42%), and 16/19 (84%). These historical carrier proportions illustrate variable expression; they are not population prevalence or individual risk predictions. The Bayesian model combines carrier observations with variant features and reports credible intervals. Method: Kroncke et al., PLOS Genet 2020; carrier study: Kroncke et al., Circ Genom Precis Med 2018.
A patented framework that fuses carrier counts, functional data, structural context and in silico predictors into a variant-level probability of disease with explicit uncertainty.
Deep mutational scanning, calibrated automated patch clamp and CRISPR-edited iPSC-cardiomyocytes measure what variants do, at the scale sequencing demands.
Large language models extract per-variant carriers and phenotypes from PubMed; a multi-model consensus scores gene–disease validity against the ClinGen SOP, with every call traceable to its source.
Our variant-level estimates give the probability that a heterozygote, on average, is affected. An individual’s risk also depends on polygenic background, sex, QTc, age and treatment. The second question is where the program is heading: patient-derived iPSC lines at the extremes of QT polygenic score, survival models of breakthrough events on therapy that we are now evaluating, and the NHGRI-funded effort to predict clinically important outcomes for people with pathogenic variants.
Free to clinicians, genetic counselors and researchers. Each gene page shows carrier counts, functional data, structural context and predictors alongside the Bayesian estimate, so the evidence behind every number can be inspected.
Long QT type 1
4,386 variants
Long QT type 2
7,995 variants
Brugada / LQT3
13,739 variants
CPVT
29,236 variants