| Configuration: AlphaMissense, BP4 ≤0.65 and PP3 ≥0.75 (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 | 87.2% accuracy percent · higher Uncertainty: 95% CI 85.4 to 88.8 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceAlphaMissense ≥0.75, 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, 'AM' group, row '≥0.75', column 'Accuracy' |
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| Configuration: AlphaMissense, BP4 ≤0.65 and PP3 ≥0.75 (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 | 95.2% negative-predictive-value percent · higher Uncertainty: 95% CI 93.8 to 96.2 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceAlphaMissense ≥0.75, 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, 'AM' group, row '≥0.75', column 'NPV' |
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| Configuration: AlphaMissense, BP4 ≤0.65 and PP3 ≥0.75 (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 | 66.7% precision percent · higher Uncertainty: 95% CI 63.0 to 70.1 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceAlphaMissense ≥0.75, 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, 'AM' group, row '≥0.75', column 'PPV' |
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| Configuration: AlphaMissense, BP4 ≤0.65 and PP3 ≥0.75 (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 | 84.3% recall percent · higher Uncertainty: 95% CI 79.9 to 88.0 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceAlphaMissense ≥0.75, 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, 'AM' group, row '≥0.75', column 'Sensitivity' |
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| Configuration: AlphaMissense, BP4 ≤0.65 and PP3 ≥0.75 (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 | 88% specificity percent · higher Uncertainty: 95% CI 86.0 to 89.8 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceAlphaMissense ≥0.75, 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, 'AM' group, row '≥0.75', column 'Specificity' |
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| Configuration: AlphaMissense, BP4 ≤0.65 and PP3 ≥0.75 (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 | −2.914 log2-likelihood-ratio unitless · lower Uncertainty: 95% CI -3.354 to -2.474 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceAlphaMissense, BP4 ≤0.65 and PP3 ≥0.75, 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 5 ('AM' group), column 'Benignity evidence (BP4): Evidence strength, log 2 LR (95% CI)' |
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| Configuration: AlphaMissense, BP4 ≤0.65 and PP3 ≥0.75 (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 | 5% proportion percent · lower Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceAlphaMissense, BP4 ≤0.65 and PP3 ≥0.75, 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 5 ('AM' group), column 'No bioinformatic code applicable' |
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| Configuration: AlphaMissense, BP4 ≤0.65 and PP3 ≥0.75 (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 | 2.81 log2-likelihood-ratio unitless · higher Uncertainty: 95% CI 2.578 to 3.042 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceAlphaMissense, BP4 ≤0.65 and PP3 ≥0.75, 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 5 ('AM' group), column 'Pathogenicity evidence (PP3): Evidence strength, log 2 LR (95% CI)' |
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