| Configuration: AlphaMissense, BP4 ≤0.34 and PP3 ≥0.56 (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 | −4.603 log2-likelihood-ratio unitless · lower Uncertainty: 95% CI -5.535 to -3.671 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceAlphaMissense, BP4 ≤0.34 and PP3 ≥0.56, 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 3 ('AM' group), column 'Benignity evidence (BP4): Evidence strength, log 2 LR (95% CI)' |
|---|
| Configuration: AlphaMissense, BP4 ≤0.34 and PP3 ≥0.56 (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 sourceAlphaMissense, BP4 ≤0.34 and PP3 ≥0.56, 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 3 ('AM' group), column 'No bioinformatic code applicable' |
|---|
| Configuration: AlphaMissense, BP4 ≤0.34 and PP3 ≥0.56 (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 | 2.08 log2-likelihood-ratio unitless · higher Uncertainty: 95% CI 1.919 to 2.247 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceAlphaMissense, BP4 ≤0.34 and PP3 ≥0.56, 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 3 ('AM' group), column 'Pathogenicity evidence (PP3): Evidence strength, log 2 LR (95% CI)' |
|---|
| Configuration: AlphaMissense, BP4 ≤0.60 and PP3 ≥0.80 (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 | −3.038 log2-likelihood-ratio unitless · lower Uncertainty: 95% CI -3.508 to -2.569 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceAlphaMissense, BP4 ≤0.60 and PP3 ≥0.80, 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 4 ('AM' group), column 'Benignity evidence (BP4): Evidence strength, log 2 LR (95% CI)' |
|---|
| Configuration: AlphaMissense, BP4 ≤0.60 and PP3 ≥0.80 (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 | 10% 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 ≤0.60 and PP3 ≥0.80, 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 4 ('AM' group), column 'No bioinformatic code applicable' |
|---|
| Configuration: AlphaMissense, BP4 ≤0.60 and PP3 ≥0.80 (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 | 3.01 log2-likelihood-ratio unitless · higher Uncertainty: 95% CI 2.746 to 3.269 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceAlphaMissense, BP4 ≤0.60 and PP3 ≥0.80, 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 4 ('AM' group), column 'Pathogenicity evidence (PP3): Evidence strength, log 2 LR (95% CI)' |
|---|
| 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' |
|---|
| 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' |
|---|
| 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' |
|---|
| 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' |
|---|
| 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' |
|---|
| 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)' |
|---|
| 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' |
|---|
| 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)' |
|---|
| Configuration: BayesDel, BP4 ≤0.15 and PP3 ≥0.28 (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 | 85.6% accuracy percent · higher Uncertainty: 95% CI 83.7 to 87.3 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceBayesDel ≥0.28, 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, 'BD' group, row '≥0.28', column 'Accuracy' |
|---|
| Configuration: BayesDel, BP4 ≤0.15 and PP3 ≥0.28 (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 | 93.8% negative-predictive-value percent · higher Uncertainty: 95% CI 92.5 to 94.9 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceBayesDel ≥0.28, 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, 'BD' group, row '≥0.28', column 'NPV' |
|---|
| Configuration: BayesDel, BP4 ≤0.15 and PP3 ≥0.28 (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 | 64.1% precision percent · higher Uncertainty: 95% CI 60.3 to 67.6 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceBayesDel ≥0.28, 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, 'BD' group, row '≥0.28', column 'PPV' |
|---|
| Configuration: BayesDel, BP4 ≤0.15 and PP3 ≥0.28 (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 | 79.8% recall percent · higher Uncertainty: 95% CI 75.1 to 84.0 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceBayesDel ≥0.28, 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, 'BD' group, row '≥0.28', column 'Sensitivity' |
|---|
| Configuration: BayesDel, BP4 ≤0.15 and PP3 ≥0.28 (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% specificity percent · higher Uncertainty: 95% CI 85.2 to 89.1 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceBayesDel ≥0.28, 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, 'BD' group, row '≥0.28', column 'Specificity' |
|---|
| Configuration: BayesDel, BP4 ≤0.15 and PP3 ≥0.28 (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 | −2.923 log2-likelihood-ratio unitless · lower Uncertainty: 95% CI -3.401 to -2.444 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceBayesDel, BP4 ≤0.15 and PP3 ≥0.28, 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 10 ('BD' group), column 'Benignity evidence (BP4): Evidence strength, log 2 LR (95% CI)' |
|---|
| Configuration: BayesDel, BP4 ≤0.15 and PP3 ≥0.28 (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 | 14% proportion percent · lower Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceBayesDel, BP4 ≤0.15 and PP3 ≥0.28, 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 10 ('BD' group), column 'No bioinformatic code applicable' |
|---|
| Configuration: BayesDel, BP4 ≤0.15 and PP3 ≥0.28 (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 | 2.64 log2-likelihood-ratio unitless · higher Uncertainty: 95% CI 2.415 to 2.872 Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceBayesDel, BP4 ≤0.15 and PP3 ≥0.28, 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 10 ('BD' group), column 'Pathogenicity evidence (PP3): Evidence strength, log 2 LR (95% CI)' |
|---|
| 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' |
|---|
| 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' |
|---|
| 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' |
|---|