| Configuration: FoldX5.0 ΔΔG on experimental PDB structures, BP4 ≤+1.5 and PP3 ≥+2.5 (Ramadane-Morchadi et al. 2025) | Protocol: BRCA1 MAVE LoF discrimination at the PP3 threshold (Ramadane-Morchadi et al. 2025 Table 2)
Dataset: BRCA1 RING and BRCT missense variants with saturation genome editing functional class (Findlay et al. 2018), LoF versus FUNC | 82.6% accuracy percent · higher Uncertainty: 95% CI 80.6 to 84.5 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceFoldX5.0 ΔΔG on experimental PDB structures ≥+2.5, BRCA1 MAVE LoF discrimination (Ramadane-Morchadi et al. 2025) brca-20261009-protocol-ramadane2025-binary Aggregation: Not reported ACMG/AMP interpretation of BRCA1 missense variants: Structure-informed scores add evidence strength granularity to the PP3/BP4 computational evidence · Table 2, 'ΔΔG PDB a' group, row '≥+2.5', column 'Accuracy' |
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| Configuration: FoldX5.0 ΔΔG on experimental PDB structures, BP4 ≤+1.5 and PP3 ≥+2.5 (Ramadane-Morchadi et al. 2025) | Protocol: BRCA1 MAVE LoF discrimination at the PP3 threshold (Ramadane-Morchadi et al. 2025 Table 2)
Dataset: BRCA1 RING and BRCT missense variants with saturation genome editing functional class (Findlay et al. 2018), LoF versus FUNC | 92% negative-predictive-value percent · higher Uncertainty: 95% CI 90.6 to 93.3 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceFoldX5.0 ΔΔG on experimental PDB structures ≥+2.5, BRCA1 MAVE LoF discrimination (Ramadane-Morchadi et al. 2025) brca-20261009-protocol-ramadane2025-binary Aggregation: Not reported ACMG/AMP interpretation of BRCA1 missense variants: Structure-informed scores add evidence strength granularity to the PP3/BP4 computational evidence · Table 2, 'ΔΔG PDB a' group, row '≥+2.5', column 'NPV' |
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| Configuration: FoldX5.0 ΔΔG on experimental PDB structures, BP4 ≤+1.5 and PP3 ≥+2.5 (Ramadane-Morchadi et al. 2025) | Protocol: BRCA1 MAVE LoF discrimination at the PP3 threshold (Ramadane-Morchadi et al. 2025 Table 2)
Dataset: BRCA1 RING and BRCT missense variants with saturation genome editing functional class (Findlay et al. 2018), LoF versus FUNC | 58.5% precision percent · higher Uncertainty: 95% CI 54.9 to 62.1 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceFoldX5.0 ΔΔG on experimental PDB structures ≥+2.5, BRCA1 MAVE LoF discrimination (Ramadane-Morchadi et al. 2025) brca-20261009-protocol-ramadane2025-binary Aggregation: Not reported ACMG/AMP interpretation of BRCA1 missense variants: Structure-informed scores add evidence strength granularity to the PP3/BP4 computational evidence · Table 2, 'ΔΔG PDB a' group, row '≥+2.5', column 'PPV' |
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| Configuration: FoldX5.0 ΔΔG on experimental PDB structures, BP4 ≤+1.5 and PP3 ≥+2.5 (Ramadane-Morchadi et al. 2025) | Protocol: BRCA1 MAVE LoF discrimination at the PP3 threshold (Ramadane-Morchadi et al. 2025 Table 2)
Dataset: BRCA1 RING and BRCT missense variants with saturation genome editing functional class (Findlay et al. 2018), LoF versus FUNC | 74.2% recall percent · higher Uncertainty: 95% CI 69.2 to 78.8 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceFoldX5.0 ΔΔG on experimental PDB structures ≥+2.5, BRCA1 MAVE LoF discrimination (Ramadane-Morchadi et al. 2025) brca-20261009-protocol-ramadane2025-binary Aggregation: Not reported ACMG/AMP interpretation of BRCA1 missense variants: Structure-informed scores add evidence strength granularity to the PP3/BP4 computational evidence · Table 2, 'ΔΔG PDB a' group, row '≥+2.5', column 'Sensitivity' |
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| Configuration: FoldX5.0 ΔΔG on experimental PDB structures, BP4 ≤+1.5 and PP3 ≥+2.5 (Ramadane-Morchadi et al. 2025) | Protocol: BRCA1 MAVE LoF discrimination at the PP3 threshold (Ramadane-Morchadi et al. 2025 Table 2)
Dataset: BRCA1 RING and BRCT missense variants with saturation genome editing functional class (Findlay et al. 2018), LoF versus FUNC | 85% specificity percent · higher Uncertainty: 95% CI 82.9 to 87.0 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceFoldX5.0 ΔΔG on experimental PDB structures ≥+2.5, BRCA1 MAVE LoF discrimination (Ramadane-Morchadi et al. 2025) brca-20261009-protocol-ramadane2025-binary Aggregation: Not reported ACMG/AMP interpretation of BRCA1 missense variants: Structure-informed scores add evidence strength granularity to the PP3/BP4 computational evidence · Table 2, 'ΔΔG PDB a' group, row '≥+2.5', column 'Specificity' |
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| Configuration: FoldX5.0 ΔΔG on experimental PDB structures, BP4 ≤+1.5 and PP3 ≥+2.5 (Ramadane-Morchadi et al. 2025) | Protocol: BRCA1 MAVE PP3/BP4 evidence strength by score threshold (Ramadane-Morchadi et al. 2025 Table 1)
Dataset: BRCA1 RING and BRCT missense variants with saturation genome editing functional class (Findlay et al. 2018), LoF versus FUNC | −2.264 log2-likelihood-ratio unitless · lower Uncertainty: 95% CI -2.632 to -1.895 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceFoldX5.0 ΔΔG on experimental PDB structures, BP4 ≤+1.5 and PP3 ≥+2.5, BRCA1 MAVE evidence strength (Ramadane-Morchadi et al. 2025) brca-20261009-protocol-ramadane2025-pp3-bp4 Aggregation: Not reported ACMG/AMP interpretation of BRCA1 missense variants: Structure-informed scores add evidence strength granularity to the PP3/BP4 computational evidence · Table 1, row 9 ('ΔΔG PDB b' group), column 'Benignity evidence (BP4): Evidence strength, log 2 LR (95% CI)' |
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| Configuration: FoldX5.0 ΔΔG on experimental PDB structures, BP4 ≤+1.5 and PP3 ≥+2.5 (Ramadane-Morchadi et al. 2025) | Protocol: BRCA1 MAVE PP3/BP4 evidence strength by score threshold (Ramadane-Morchadi et al. 2025 Table 1)
Dataset: BRCA1 RING and BRCT missense variants with saturation genome editing functional class (Findlay et al. 2018), LoF versus FUNC | 12% proportion percent · lower Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceFoldX5.0 ΔΔG on experimental PDB structures, BP4 ≤+1.5 and PP3 ≥+2.5, BRCA1 MAVE evidence strength (Ramadane-Morchadi et al. 2025) brca-20261009-protocol-ramadane2025-pp3-bp4 Aggregation: Not reported ACMG/AMP interpretation of BRCA1 missense variants: Structure-informed scores add evidence strength granularity to the PP3/BP4 computational evidence · Table 1, row 9 ('ΔΔG PDB b' group), column 'No bioinformatic code applicable' |
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| Configuration: FoldX5.0 ΔΔG on experimental PDB structures, BP4 ≤+1.5 and PP3 ≥+2.5 (Ramadane-Morchadi et al. 2025) | Protocol: BRCA1 MAVE PP3/BP4 evidence strength by score threshold (Ramadane-Morchadi et al. 2025 Table 1)
Dataset: BRCA1 RING and BRCT missense variants with saturation genome editing functional class (Findlay et al. 2018), LoF versus FUNC | 2.31 log2-likelihood-ratio unitless · higher Uncertainty: 95% CI 2.093 to 2.525 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceFoldX5.0 ΔΔG on experimental PDB structures, BP4 ≤+1.5 and PP3 ≥+2.5, BRCA1 MAVE evidence strength (Ramadane-Morchadi et al. 2025) brca-20261009-protocol-ramadane2025-pp3-bp4 Aggregation: Not reported ACMG/AMP interpretation of BRCA1 missense variants: Structure-informed scores add evidence strength granularity to the PP3/BP4 computational evidence · Table 1, row 9 ('ΔΔG PDB b' group), column 'Pathogenicity evidence (PP3): Evidence strength, log 2 LR (95% CI)' |
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