Configuration

MSC-PolyPhen2-based (Cubuk et al. 2021)

MSC scores dichotomised at the cited threshold.

Overview

MSC scores dichotomised at the cited threshold.

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Evaluations and results

2 evaluations · 5 results. Different protocols are not a single leaderboard.

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Exact evaluated configurations and original reported results
Tested configuration	Protocol and dataset	Finding	Evidence and details
Configuration: MSC-PolyPhen2-based (Cubuk et al. 2021)	Protocol: BRCA1 functional truth set, binary in silico calls (Cubuk et al. 2021) Dataset: BRCA1 functional truth set: 1641 missense variants classed deleterious or tolerated by HAP1 cell survival after saturation genome editing	11.4 benignity-likelihood-ratio unitless · higher Uncertainty: Sources conflict: Printed interval (11.1-11.7) has the same log-scale width as this row's positive likelihood ratio interval and is not consistent with the Supplementary Table 6 counts; kept in printed_source_cell only. Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source MSC-PolyPhen2-based on the BRCA1 functional truth set (Cubuk et al. 2021) brca-20261009-protocol-cubuk2021-brca1 Aggregation: Not reported Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes; Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx) · Supplementary Table 9 (sheet 'SupTable9_Likelihood_Ratios'), G44; tool 'MSC-PolyPhen2-based'; column 'BRCA1_negative_LR'
Configuration: MSC-PolyPhen2-based (Cubuk et al. 2021)	Protocol: BRCA1 functional truth set, binary in silico calls (Cubuk et al. 2021) Dataset: BRCA1 functional truth set: 1641 missense variants classed deleterious or tolerated by HAP1 cell survival after saturation genome editing	5 false-negative-count count · lower Uncertainty: Not applicable: Count Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source MSC-PolyPhen2-based on the BRCA1 functional truth set (Cubuk et al. 2021) brca-20261009-protocol-cubuk2021-brca1 Aggregation: Not reported Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes; Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx) · Supplementary Table 6 (sheet 'SupTable6_Tool_Counts'), L37; tool 'MSC-PolyPhen2-based'; column 'BRCA1_FN'
Configuration: MSC-PolyPhen2-based (Cubuk et al. 2021)	Protocol: BRCA1 functional truth set, binary in silico calls (Cubuk et al. 2021) Dataset: BRCA1 functional truth set: 1641 missense variants classed deleterious or tolerated by HAP1 cell survival after saturation genome editing	1.16 likelihood-ratio unitless · higher Uncertainty: CI 1.13 to 1.19. Interval level and method not printed. Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source MSC-PolyPhen2-based on the BRCA1 functional truth set (Cubuk et al. 2021) brca-20261009-protocol-cubuk2021-brca1 Aggregation: Not reported Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes; Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx) · Supplementary Table 9 (sheet 'SupTable9_Likelihood_Ratios'), F44; tool 'MSC-PolyPhen2-based'; column 'BRCA1_positive_LR'
Configuration: MSC-PolyPhen2-based (Cubuk et al. 2021)	Protocol: BRCA2 functional truth set, binary in silico calls (Cubuk et al. 2021) Dataset: BRCA2 functional truth set: 188 missense variants classed deleterious or tolerated by Homology-directed repair	0 false-negative-count count · lower Uncertainty: Not applicable: Count Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source MSC-PolyPhen2-based on the BRCA2 functional truth set (Cubuk et al. 2021) brca-20261009-protocol-cubuk2021-brca2 Aggregation: Not reported Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes; Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx) · Supplementary Table 6 (sheet 'SupTable6_Tool_Counts'), U37; tool 'MSC-PolyPhen2-based'; column 'BRCA2_FN'
Configuration: MSC-PolyPhen2-based (Cubuk et al. 2021)	Protocol: BRCA2 functional truth set, binary in silico calls (Cubuk et al. 2021) Dataset: BRCA2 functional truth set: 188 missense variants classed deleterious or tolerated by Homology-directed repair	1 likelihood-ratio unitless · higher Uncertainty: CI 0.992 to 1.02. Interval level and method not printed. Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source MSC-PolyPhen2-based on the BRCA2 functional truth set (Cubuk et al. 2021) brca-20261009-protocol-cubuk2021-brca2 Aggregation: Not reported Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes; Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx) · Supplementary Table 9 (sheet 'SupTable9_Likelihood_Ratios'), H44; tool 'MSC-PolyPhen2-based'; column 'BRCA2_positive_LR'

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Sources and history

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2 source records and release history

Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes · Original source · Genetics in Medicine 23(11):2096, published 2021-07-06; PMC8553612 full-text XML
Cubuk et al. 2021, Supplementary tables 1-13 (41436_2021_1265_MOESM3_ESM.xlsx) · Original source · 41436_2021_1265_MOESM3_ESM.xlsx

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Technical metadata and extraction receipts

Stable ID: brca-20261009-config-cubuk2021-msc-polyphen2-based

areas: dna-genomes
contexts: clinical_research
method types: specialist
reported name: MSC-PolyPhen2-based
foundation model eligible: false
protocol: Discretisation: TOL (low); VUS (unknown); DEL (high)
source locator: Supplementary Table 5 row 38 ('MSC', 'MSC_PolyPhen2')
missing metadata: version: reason: unreported; note: Score source: MSC webserver (http://pec630.rockefeller.edu:8080/MSC/)

Related records

configuration of: Mutation significance cutoff (MSC)
uses model: PolyPhen-2
system: MSC-PolyPhen2-based on the BRCA1 functional truth set (Cubuk et al. 2021)
system: MSC-PolyPhen2-based on the BRCA2 functional truth set (Cubuk et al. 2021)

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