| Configuration: FoldX5.0 ΔΔG on AlphaFold2 models, BP4 ≤+1.0 and PP3 ≥+3.0 (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 | 86.6% accuracy percent · higher Uncertainty: 95% CI 84.6 to 88.4 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceFoldX5.0 ΔΔG on AlphaFold2 models ≥+3, 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 '≥+3', column 'Accuracy' |
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| Configuration: FoldX5.0 ΔΔG on AlphaFold2 models, BP4 ≤+1.0 and PP3 ≥+3.0 (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 | 96.6% negative-predictive-value percent · higher Uncertainty: Sources conflict: Printed interval (92.3-97.5) is inconsistent with the estimate: an NPV of 96.6% over about 1,050 predicted-FUNC variants gives roughly 95.4 to 97.6, and every other Table 2 interval is close to symmetric. The lower bound is probably misprinted; the interval is kept in printed_source_cell only. Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceFoldX5.0 ΔΔG on AlphaFold2 models ≥+3, 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 '≥+3', column 'NPV' |
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| Configuration: FoldX5.0 ΔΔG on AlphaFold2 models, BP4 ≤+1.0 and PP3 ≥+3.0 (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 | 64% precision percent · higher Uncertainty: 95% CI 60.2 to 67.6 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceFoldX5.0 ΔΔG on AlphaFold2 models ≥+3, 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 '≥+3', column 'PPV' |
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| Configuration: FoldX5.0 ΔΔG on AlphaFold2 models, BP4 ≤+1.0 and PP3 ≥+3.0 (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 | 89.1% recall percent · higher Uncertainty: 95% CI 84.9 to 92.5 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceFoldX5.0 ΔΔG on AlphaFold2 models ≥+3, 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 '≥+3', column 'Sensitivity' |
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| Configuration: FoldX5.0 ΔΔG on AlphaFold2 models, BP4 ≤+1.0 and PP3 ≥+3.0 (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 | 85.9% specificity percent · higher Uncertainty: 95% CI 83.5 to 88.0 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceFoldX5.0 ΔΔG on AlphaFold2 models ≥+3, 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 '≥+3', column 'Specificity' |
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| Configuration: FoldX5.0 ΔΔG on AlphaFold2 models, BP4 ≤+1.0 and PP3 ≥+3.0 (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 | −3.417 log2-likelihood-ratio unitless · lower Uncertainty: 95% CI -4.051 to -2.784 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceFoldX5.0 ΔΔG on AlphaFold2 models, BP4 ≤+1.0 and PP3 ≥+3.0, 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 6 ('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 ≤+1.0 and PP3 ≥+3.0 (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 | 26% 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 ≤+1.0 and PP3 ≥+3.0, 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 6 ('ΔΔG AF b' group), column 'No bioinformatic code applicable' |
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| Configuration: FoldX5.0 ΔΔG on AlphaFold2 models, BP4 ≤+1.0 and PP3 ≥+3.0 (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 | 2.69 log2-likelihood-ratio unitless · higher Uncertainty: 95% CI 2.448 to 2.933 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceFoldX5.0 ΔΔG on AlphaFold2 models, BP4 ≤+1.0 and PP3 ≥+3.0, 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 6 ('ΔΔG AF b' group), column 'Pathogenicity evidence (PP3): Evidence strength, log 2 LR (95% CI)' |
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