P658: Causal necessity as a framework for genome interpretation and molecular diagnosis
Abstract
If a clinical genetic test yields a pathogenic variant in a gene associated with a specific disease, an analyst or provider may judge the case as “solved.” That final interpretation takes into account the full clinical context and rests primarily on clinical judgment. But how certain can we be that a molecular diagnosis has been achieved in the individual case? In this study, we use the Probability of Necessity (PN) as a measure of diagnostic certainty. PN is defined as the probability that the disease would not have occurred without the variant, given that both the disease and the variant have been observed in the individual patient.
Fields of Study & Subjects
Genomics and Rare Diseases
Genetic Associations and Epidemiology
Clinical Reasoning and Diagnostic Skills
Publication details
- Journal / source
- Genetics in Medicine Open
- Volume
- 4
- Pages
- 104148–104148
- Publication date
- 1 January 2026
- Language
- EN