| Title: |
Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes. |
| Authors: |
Cubuk, C; Garrett, A; Choi, S; King, L; Loveday, C; Torr, B; Burghel, GJ; Durkie, M; Callaway, A; Robinson, R; Drummond, J; Berry, I; Wallace, A; Eccles, D; Tischkowitz, M; Whiffin, N; Ware, JS; Hanson, H; Turnbull, C; CanVIG-Uk |
| Contributors: |
Garrett, Alice; Choi, Subin; Pemberton - Whiteley, Bethany; Turnbull, Clare |
| Publisher Information: |
ELSEVIER SCIENCE INC |
| Publication Year: |
2021 |
| Collection: |
The Institute of Cancer Research (ICR): Publications Repository |
| Description: |
PURPOSE: Where multiple in silico tools are concordant, the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) framework affords supporting evidence toward pathogenicity or benignity, equivalent to a likelihood ratio of ~2. However, limited availability of "clinical truth sets" and prior use in tool training limits their utility for evaluation of tool performance. METHODS: We created a truth set of 9,436 missense variants classified as deleterious or tolerated in clinically validated high-throughput functional assays for BRCA1, BRCA2, MSH2, PTEN, and TP53 to evaluate predictive performance for 44 recommended/commonly used in silico tools. RESULTS: Over two-thirds of the tool-threshold combinations examined had specificity of |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
1530-0366; 1098-3600 |
| Relation: |
Genetics in Medicine; https://repository.icr.ac.uk/handle/internal/4673 |
| Availability: |
https://repository.icr.ac.uk/handle/internal/4681; https://repository.icr.ac.uk/handle/internal/4673 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 |
| Accession Number: |
edsbas.15BF0B1A |
| Database: |
BASE |