For complex pancreatic disease VARIANT PATHOGENICITY EVALUATION, what types of evidence shall be included? How shall the levels of evidence be defined in terms of gene dysfunction, clinical context, biomarkers, clinical disease features, and other evidences?
Considerations: How should investigators and clinicians interpret MAF, computer predictions, molecular modeling, clinical evidence, animal models, biomarker evidence, etc. Define “pathogenic” or “mutation of variable clinical significance” more accurately. How should genetic (clinical) evidence= association, effect size, p value, replications be quantify and qualified? Functional evidence (define and quantify strength of evidence different levels) i.e. predictions, modeling, biochemical, cell biological (test tube, cell culture), animal models. Should pathogenicity be quantified with a score based on the genetic and functional evidence. Should labels such as modifier or variable significance be used, or just labeling variants as pathogenic, neutral or protective and add quantitative descriptors (scores).