| Configuration: FoldX5.0 ΔΔG on AlphaFold2 models, 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 | 83.7% accuracy percent · higher Uncertainty: 95% CI 81.7 to 85.4 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceFoldX5.0 ΔΔG on AlphaFold2 models ≥+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 AF a' group, row '≥+2.5', column 'Accuracy' |
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| Configuration: FoldX5.0 ΔΔG on AlphaFold2 models, 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 | 94.1% negative-predictive-value percent · higher Uncertainty: 95% CI 92.8 to 95.3 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceFoldX5.0 ΔΔG on AlphaFold2 models ≥+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 AF a' group, row '≥+2.5', column 'NPV' |
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| Configuration: FoldX5.0 ΔΔG on AlphaFold2 models, 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 | 59.5% precision percent · higher Uncertainty: 95% CI 56.1 to 62.8 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceFoldX5.0 ΔΔG on AlphaFold2 models ≥+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 AF a' group, row '≥+2.5', column 'PPV' |
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| Configuration: FoldX5.0 ΔΔG on AlphaFold2 models, 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 | 81.6% recall percent · higher Uncertainty: 95% CI 77.1 to 85.6 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceFoldX5.0 ΔΔG on AlphaFold2 models ≥+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 AF a' group, row '≥+2.5', column 'Sensitivity' |
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| Configuration: FoldX5.0 ΔΔG on AlphaFold2 models, 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 | 84.2% specificity percent · higher Uncertainty: 95% CI 81.2 to 86.2 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceFoldX5.0 ΔΔG on AlphaFold2 models ≥+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 AF a' group, row '≥+2.5', column 'Specificity' |
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| Configuration: FoldX5.0 ΔΔG on AlphaFold2 models, 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 | −2.946 log2-likelihood-ratio unitless · lower Uncertainty: 95% CI -3.433 to -2.456 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceFoldX5.0 ΔΔG on AlphaFold2 models, 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 7 ('ΔΔG AF b' group), column 'Benignity evidence (BP4): Evidence strength, log 2 LR (95% CI)' |
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| Configuration: FoldX5.0 ΔΔG on AlphaFold2 models, 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 | 8% 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 AlphaFold2 models, 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 7 ('ΔΔG AF b' group), column 'No bioinformatic code applicable' |
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| Configuration: FoldX5.0 ΔΔG on AlphaFold2 models, 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 | 2.37 log2-likelihood-ratio unitless · higher Uncertainty: 95% CI 2.164 to 2.570 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceFoldX5.0 ΔΔG on AlphaFold2 models, 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 7 ('ΔΔG AF b' group), column 'Pathogenicity evidence (PP3): Evidence strength, log 2 LR (95% CI)' |
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