Connor Donegan, Yongwan Chun, Daniel A Griffith
Modeling Community Health with Areal Data: Bayesian Inference with Survey Standard Errors and Spatial Structure
International journal of environmental research and public health
pathogenic constitutional apc variants underlie familial adenomatous polyposis common hereditary gastrointestinal polyposis syndrome improve variant classification resolve interpretative challenges variants uncertain significance vus apcspecific acmgamp variant classification criteria developed clingeninsight hereditary colorectal cancerpolyposis variant curation expert panel vcep streamlined algorithm using apc specific criteria developed applied assess apc variants clinvar insight international reference apc lovd variant database total 10228 unique apc variants analysed among clinvar lovd variants initial classification likely benign likely pathogenic 94 96 remained original categories respectively contrast 41 clinvar 61 lovd vus reclassified clinically actionable classes vast majority likely benign total number vus reduced 37 21 36 58 promising apc variants remained vus despite evidence pathogenicity data miningdriven workup allowed reclassification likely pathogenic application apc specific criteria substantially reduced number vus clinvar lovd study also demonstrated feasibility systematic approach variant classification large datasets might serve generalisable model genediseasespecific variant interpretation initiatives also allowed prioritization vus benefit indepth evidence collection subset apc variants approved vcep made publicly available clinvar lovd widespread clinical use