Structural Evaluation of <i>RYR2</i> -CPVT Missense Variants and Continuous Bayesian Estimates of Their Penetrance
Traditional categorical variant annotations limit accurate disease risk assessment, especially in populations unascertained for disease. A probabilistic, population-calibrated penetrance framework enables more meaningful prospective variant interpretation. Our Bayesian CPVT-prior outperforms current tools in evaluating RYR2 variant penetrance. We provide prospective Bayesian CPVT penetrance values for 29 242 RYR2 missense variants at our online variant browser.
Authors
- Bjorn K Knollmann
- Brett M. Kroncke
- Jeffrey Schmeckpeper (ORCID: https://orcid.org/0000-0001-9437-5871)
- Loren Vanags
- Matthew J. O’Neill (ORCID: https://orcid.org/0000-0003-2014-7950)
- Kohei Yamauchi
- Kundivy Dauda
- Devyn W. Mitchell
- Alex Shen
- Prince J. Kannankeril
- Matthew Ku
Institutions
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Shiga University of Medical Science (JP)
- Monroe Carell Jr. Children's Hospital (US)
Publication Details
- Journal
- Circulation Genomic and Precision Medicine
- Published
- 2026-03-27
- DOI
- https://doi.org/10.1161/circgen.125.005457
- Primary Topic
- Genomics and Rare Diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.00