{"id":"W4415708527","doi":"10.1126/science.ady7186","title":"The functional landscape of coding variation in the familial hypercholesterolemia gene <i>LDLR</i>","year":2025,"lang":"en","type":"article","venue":"Science","topic":"Lipoproteins and Cardiovascular Health","field":"Medicine","cited_by":21,"is_retracted":false,"has_abstract":true,"ca_institutions":"Western University; Robarts Clinical Trials; Lunenfeld-Tanenbaum Research Institute; University of Toronto","funders":"","keywords":"Familial hypercholesterolemia; Missense mutation; Hyperlipidemia; Gene; Phenotype; Disease; Limiting; LDL receptor; Multifactorial Inheritance","routes":{"ca_aff":true,"ca_fund":false,"ca_venue":false,"about_ca":false,"invisible_to_affiliation_only":false},"retraction":null,"screen":null,"direct_labels":[],"prediction":{"model_version":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0006925202,0.0003004293,0.0002812747,0.0007119577,0.0003685656,0.0005990178,0.00020462,0.000362175,0.0020951],"category_scores_gemma":[0.001680332,0.0001258842,0.0003999199,0.0007831305,0.0003770741,0.0001962114,0.0003198845,0.0004281501,0.0002899745],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0002264216,"about_ca_system_score_gemma":0.0002280726,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.005581323,"about_ca_topic_score_gemma":0.008146132,"domain_scores_codex":[0.9994579,0.0001927354,0.00003015211,0.0001918793,0.00006506734,0.00006229991],"domain_scores_gemma":[0.9993181,0.000356843,0.000143098,0.00007415515,0.000045308,0.00006260398],"domain_codex":null,"domain_gemma":null,"domain_candidate":null,"domain_consensus":null,"study_design_codex":"observational","study_design_gemma":"observational","study_design_scores_codex":[0.001539677,0.0001319005,0.6968926,0.000186885,0.001359342,0.001683513,0.0007774097,0.008666327,0.2249889,0.006151978,0.002157022,0.05546446],"study_design_scores_gemma":[0.00007765778,0.0003636481,0.9545197,0.00006303564,0.000643375,0.001964232,0.0003192014,0.0207558,0.009374762,0.006922045,0.004925353,0.00007130079],"study_design_candidate":"observational","study_design_consensus":"observational","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9952303,0.0002951121,0.002654527,0.0001390874,0.000007543214,0.000003685367,0.0009159885,0.00003690215,0.0007167882],"genre_scores_gemma":[0.9979954,0.000101343,0.001025062,0.00008136184,0.000005825178,0.000004184717,0.0005815331,0.00002049569,0.0001848841],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.005581323,"threshold_uncertainty_score":0.01109767,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.01443618082610563,"score_gpt":0.264623044738005,"score_spread":0.2501868639118994,"validation_status":"score_only:v0-immature-baseline","note":"Baseline scores from an immature model (maturity gate not passed). Scores rank; they never assert a category."}}