{ "checked": "2026-11-14", "policy": "rfp19-1/2026-11-14", "geneSplit": { "development": [ "APC", "CDKL5", "CYP1B1", "DYSF", "F9", "FBN1", "GAA", "GAMT", "GFAP", "GUCY2D", "HNF1A", "HNF4A", "IDUA", "ITGA2B", "MECP2", "MYH7", "PAH", "RPE65", "RYR1", "VWF" ], "heldOut": [ "ABCA4", "ACADVL", "ATM", "BMPR2", "CAPN3", "CDH1", "DCLRE1C", "DICER1", "F8", "GALT", "GCK", "ITGB3", "MYOC", "PTEN", "RPGR", "RS1", "RUNX1", "SERPINC1", "SLC6A8", "TP53" ] }, "ruleEngineAgainstExpertRecords": { "recordsWithParsableCodes": 8667, "unparsedCodes": {}, "sameClassByTable5WithSviRule": { "count": 8257, "of": 8667, "percent": 95.27, "interval95": [ 94.8, 95.7 ] }, "sameClassByPoints": { "count": 8235, "of": 8667, "percent": 95.02, "interval95": [ 94.54, 95.45 ] }, "expertToTableDifferences": { "Likely benign -> Uncertain significance": 220, "Uncertain significance -> Likely benign": 68, "Pathogenic -> Likely pathogenic": 40, "Uncertain significance -> Likely pathogenic": 22, "Likely benign -> Benign": 18, "Likely pathogenic -> Pathogenic": 16, "Benign -> Likely benign": 14, "Likely pathogenic -> Uncertain significance": 7, "Uncertain significance -> Benign": 3, "Pathogenic -> Uncertain significance": 1, "Uncertain significance -> Pathogenic": 1 } }, "blindVariantClassification": { "auditGate": { "gate": "pass", "criteriaClaimed": 17504, "criteriaAccepted": 17504, "criteriaBlocked": 0, "blockedByReason": {}, "classificationMismatches": 0 }, "all": { "variants": 8667, "genes": 40, "sensitivityPathogenicOrLikely": { "count": 1896, "of": 4002, "percent": 47.38, "interval95": [ 45.83, 48.93 ] }, "specificityAgainstBenignOrLikely": { "count": 2004, "of": 2009, "percent": 99.75, "interval95": [ 99.42, 99.89 ] }, "expertUncertainCalledPathogenicOrLikely": { "count": 181, "of": 2656, "percent": 6.81, "interval95": [ 5.92, 7.84 ] }, "expertPathogenicCalledBenignOrLikely": { "count": 1, "of": 4002, "percent": 0.02, "interval95": [ 0.0, 0.14 ] }, "expertBenignCalledBenignOrLikely": { "count": 790, "of": 2009, "percent": 39.32, "interval95": [ 37.21, 41.48 ] }, "expertClassVsPipelineClass": { "Pathogenic": { "Pathogenic": 15, "Likely pathogenic": 1286, "Uncertain significance": 1006, "Likely benign": 1, "Benign": 0 }, "Likely pathogenic": { "Pathogenic": 4, "Likely pathogenic": 591, "Uncertain significance": 1099, "Likely benign": 0, "Benign": 0 }, "Uncertain significance": { "Pathogenic": 0, "Likely pathogenic": 181, "Uncertain significance": 2416, "Likely benign": 59, "Benign": 0 }, "Likely benign": { "Pathogenic": 0, "Likely pathogenic": 2, "Uncertain significance": 751, "Likely benign": 453, "Benign": 2 }, "Benign": { "Pathogenic": 0, "Likely pathogenic": 3, "Uncertain significance": 463, "Likely benign": 169, "Benign": 166 } }, "byGroup": { "consequence:missense": { "sensitivity": { "count": 699, "of": 2055, "percent": 34.01, "interval95": [ 32.0, 36.09 ] }, "specificity": { "count": 802, "of": 806, "percent": 99.5, "interval95": [ 98.73, 99.81 ] } }, "consequence:null": { "sensitivity": { "count": 1197, "of": 1657, "percent": 72.24, "interval95": [ 70.03, 74.34 ] }, "specificity": { "count": 11, "of": 12, "percent": 91.67, "interval95": [ 64.61, 98.51 ] } }, "consequence:other": { "sensitivity": { "count": 0, "of": 290, "percent": 0.0, "interval95": [ 0.0, 1.31 ] }, "specificity": { "count": 1191, "of": 1191, "percent": 100.0, "interval95": [ 99.68, 100.0 ] } }, "gnomad:absent": { "sensitivity": { "count": 1103, "of": 2016, "percent": 54.71, "interval95": [ 52.53, 56.87 ] }, "specificity": { "count": 315, "of": 316, "percent": 99.68, "interval95": [ 98.23, 99.94 ] } }, "gnomad:listed": { "sensitivity": { "count": 793, "of": 1986, "percent": 39.93, "interval95": [ 37.8, 42.1 ] }, "specificity": { "count": 1689, "of": 1693, "percent": 99.76, "interval95": [ 99.39, 99.91 ] } } }, "criteriaAgainstExpertRecords": { "PVS1": { "pipelineApplied": 1767, "expertApplied": 1802, "both": 1700, "pipelineAlsoInExpertPercent": 96.21, "expertAlsoInPipelinePercent": 94.34 }, "PS1": { "pipelineApplied": 89, "expertApplied": 128, "both": 34, "pipelineAlsoInExpertPercent": 38.2, "expertAlsoInPipelinePercent": 26.56 }, "PM2": { "pipelineApplied": 7209, "expertApplied": 6048, "both": 5828, "pipelineAlsoInExpertPercent": 80.84, "expertAlsoInPipelinePercent": 96.36 }, "PM4": { "pipelineApplied": 166, "expertApplied": 159, "both": 106, "pipelineAlsoInExpertPercent": 63.86, "expertAlsoInPipelinePercent": 66.67 }, "PM5": { "pipelineApplied": 1364, "expertApplied": 979, "both": 614, "pipelineAlsoInExpertPercent": 45.01, "expertAlsoInPipelinePercent": 62.72 }, "PP2": { "pipelineApplied": 1390, "expertApplied": 435, "both": 433, "pipelineAlsoInExpertPercent": 31.15, "expertAlsoInPipelinePercent": 99.54 }, "PP3": { "pipelineApplied": 3023, "expertApplied": 2798, "both": 2463, "pipelineAlsoInExpertPercent": 81.48, "expertAlsoInPipelinePercent": 88.03 }, "BA1": { "pipelineApplied": 168, "expertApplied": 645, "both": 165, "pipelineAlsoInExpertPercent": 98.21, "expertAlsoInPipelinePercent": 25.58 }, "BS1": { "pipelineApplied": 251, "expertApplied": 475, "both": 38, "pipelineAlsoInExpertPercent": 15.14, "expertAlsoInPipelinePercent": 8.0 }, "BP4": { "pipelineApplied": 1371, "expertApplied": 1810, "both": 1022, "pipelineAlsoInExpertPercent": 74.54, "expertAlsoInPipelinePercent": 56.46 }, "BP7": { "pipelineApplied": 706, "expertApplied": 875, "both": 549, "pipelineAlsoInExpertPercent": 77.76, "expertAlsoInPipelinePercent": 62.74 }, "BA1 or BS1": { "pipelineApplied": 419, "expertApplied": 1120, "both": 406, "pipelineAlsoInExpertPercent": 96.9, "expertAlsoInPipelinePercent": 36.25 } } }, "development": { "variants": 3817, "genes": 20, "sensitivityPathogenicOrLikely": { "count": 912, "of": 2112, "percent": 43.18, "interval95": [ 41.08, 45.3 ] }, "specificityAgainstBenignOrLikely": { "count": 681, "of": 685, "percent": 99.42, "interval95": [ 98.51, 99.77 ] }, "expertUncertainCalledPathogenicOrLikely": { "count": 104, "of": 1020, "percent": 10.2, "interval95": [ 8.49, 12.2 ] }, "expertPathogenicCalledBenignOrLikely": { "count": 0, "of": 2112, "percent": 0.0, "interval95": [ 0.0, 0.18 ] }, "expertBenignCalledBenignOrLikely": { "count": 286, "of": 685, "percent": 41.75, "interval95": [ 38.11, 45.48 ] } }, "heldOut": { "variants": 4850, "genes": 20, "sensitivityPathogenicOrLikely": { "count": 984, "of": 1890, "percent": 52.06, "interval95": [ 49.81, 54.31 ] }, "specificityAgainstBenignOrLikely": { "count": 1323, "of": 1324, "percent": 99.92, "interval95": [ 99.57, 99.99 ] }, "expertUncertainCalledPathogenicOrLikely": { "count": 77, "of": 1636, "percent": 4.71, "interval95": [ 3.78, 5.84 ] }, "expertPathogenicCalledBenignOrLikely": { "count": 1, "of": 1890, "percent": 0.05, "interval95": [ 0.01, 0.3 ] }, "expertBenignCalledBenignOrLikely": { "count": 504, "of": 1324, "percent": 38.07, "interval95": [ 35.49, 40.71 ] } } }, "simulatedPanelCases": { "phenotypeTermsUsed": "noisy", "variantsCarriedPerCase": { "median": 127.0, "min": 106, "max": 147 }, "auditGate": { "criteriaClaimed": 147363, "criteriaBlocked": 0, "classificationMismatches": 0 }, "all": { "cases": 480, "genes": 40, "sensitivity": { "count": 124, "of": 240, "percent": 51.67, "interval95": [ 45.37, 57.91 ] }, "specificity": { "count": 240, "of": 240, "percent": 100.0, "interval95": [ 98.42, 100.0 ] }, "casesWithAnotherGeneCalled": [], "spikedVariantClasses": { "Likely pathogenic": 92, "Pathogenic": 72, "Uncertain significance": 106 }, "phenotypeRankOfTrueGene": { "precise": { "medianRank": 1.0, "top1": { "count": 240, "of": 240, "percent": 100.0, "interval95": [ 98.42, 100.0 ] }, "top10": { "count": 240, "of": 240, "percent": 100.0, "interval95": [ 98.42, 100.0 ] } }, "imprecise": { "medianRank": 1.0, "top1": { "count": 240, "of": 240, "percent": 100.0, "interval95": [ 98.42, 100.0 ] }, "top10": { "count": 240, "of": 240, "percent": 100.0, "interval95": [ 98.42, 100.0 ] } }, "noisy": { "medianRank": 1.0, "top1": { "count": 157, "of": 240, "percent": 65.42, "interval95": [ 59.2, 71.15 ] }, "top10": { "count": 194, "of": 240, "percent": 80.83, "interval95": [ 75.38, 85.31 ] } } }, "sensitivityByDesign": { "compound heterozygous trio": { "count": 15, "of": 30, "percent": 50.0, "interval95": [ 33.15, 66.85 ] }, "de novo trio": { "count": 48, "of": 75, "percent": 64.0, "interval95": [ 52.7, 73.94 ] }, "heterozygous singleton": { "count": 26, "of": 54, "percent": 48.15, "interval95": [ 35.39, 61.15 ] }, "homozygous singleton": { "count": 15, "of": 30, "percent": 50.0, "interval95": [ 33.15, 66.85 ] }, "homozygous trio": { "count": 11, "of": 30, "percent": 36.67, "interval95": [ 21.87, 54.49 ] }, "maternal carrier trio": { "count": 9, "of": 21, "percent": 42.86, "interval95": [ 24.47, 63.45 ] } }, "sensitivityByInheritance": { "AD": { "count": 64, "of": 108, "percent": 59.26, "interval95": [ 49.83, 68.05 ] }, "AR": { "count": 41, "of": 90, "percent": 45.56, "interval95": [ 35.66, 55.82 ] }, "XL": { "count": 19, "of": 42, "percent": 45.24, "interval95": [ 31.22, 60.05 ] } } }, "development": { "cases": 240, "genes": 20, "sensitivity": { "count": 66, "of": 120, "percent": 55.0, "interval95": [ 46.08, 63.61 ] }, "specificity": { "count": 120, "of": 120, "percent": 100.0, "interval95": [ 96.9, 100.0 ] }, "casesWithAnotherGeneCalled": [], "spikedVariantClasses": { "Likely pathogenic": 48, "Pathogenic": 37, "Uncertain significance": 53 }, "phenotypeRankOfTrueGene": { "precise": { "medianRank": 1.0, "top1": { "count": 120, "of": 120, "percent": 100.0, "interval95": [ 96.9, 100.0 ] }, "top10": { "count": 120, "of": 120, "percent": 100.0, "interval95": [ 96.9, 100.0 ] } }, "imprecise": { "medianRank": 1.0, "top1": { "count": 120, "of": 120, "percent": 100.0, "interval95": [ 96.9, 100.0 ] }, "top10": { "count": 120, "of": 120, "percent": 100.0, "interval95": [ 96.9, 100.0 ] } }, "noisy": { "medianRank": 1.0, "top1": { "count": 79, "of": 120, "percent": 65.83, "interval95": [ 56.97, 73.71 ] }, "top10": { "count": 102, "of": 120, "percent": 85.0, "interval95": [ 77.53, 90.3 ] } } } }, "heldOut": { "cases": 240, "genes": 20, "sensitivity": { "count": 58, "of": 120, "percent": 48.33, "interval95": [ 39.58, 57.19 ] }, "specificity": { "count": 120, "of": 120, "percent": 100.0, "interval95": [ 96.9, 100.0 ] }, "casesWithAnotherGeneCalled": [], "spikedVariantClasses": { "Likely pathogenic": 44, "Pathogenic": 35, "Uncertain significance": 53 }, "phenotypeRankOfTrueGene": { "precise": { "medianRank": 1.0, "top1": { "count": 120, "of": 120, "percent": 100.0, "interval95": [ 96.9, 100.0 ] }, "top10": { "count": 120, "of": 120, "percent": 100.0, "interval95": [ 96.9, 100.0 ] } }, "imprecise": { "medianRank": 1.0, "top1": { "count": 120, "of": 120, "percent": 100.0, "interval95": [ 96.9, 100.0 ] }, "top10": { "count": 120, "of": 120, "percent": 100.0, "interval95": [ 96.9, 100.0 ] } }, "noisy": { "medianRank": 1.0, "top1": { "count": 78, "of": 120, "percent": 65.0, "interval95": [ 56.12, 72.95 ] }, "top10": { "count": 92, "of": 120, "percent": 76.67, "interval95": [ 68.34, 83.33 ] } } } } }, "auditGateFaultInjection": { "casesUsed": 120, "faultsInjected": 9493, "faultsStopped": { "count": 9493, "of": 9493, "percent": 100.0, "interval95": [ 99.96, 100.0 ] }, "byFault": { "classification_mismatch": { "injected": 487, "stopped": 487, "stoppedWithExpectedReason": 487, "classUnchangedWhereRequired": 487, "classCheckRequired": 487, "otherVariantsUntouched": 487, "gateBlocked": 487 }, "double_counting": { "injected": 122, "stopped": 122, "stoppedWithExpectedReason": 122, "classUnchangedWhereRequired": 122, "classCheckRequired": 122, "otherVariantsUntouched": 122, "gateBlocked": 122 }, "duplicate_code": { "injected": 462, "stopped": 462, "stoppedWithExpectedReason": 462, "classUnchangedWhereRequired": 462, "classCheckRequired": 462, "otherVariantsUntouched": 462, "gateBlocked": 462 }, "evidence_kind_missing": { "injected": 487, "stopped": 487, "stoppedWithExpectedReason": 487, "classUnchangedWhereRequired": 487, "classCheckRequired": 487, "otherVariantsUntouched": 487, "gateBlocked": 487 }, "evidence_not_in_ledger": { "injected": 924, "stopped": 924, "stoppedWithExpectedReason": 924, "otherVariantsUntouched": 924, "gateBlocked": 924 }, "evidence_out_of_scope": { "injected": 487, "stopped": 487, "stoppedWithExpectedReason": 487, "classUnchangedWhereRequired": 487, "classCheckRequired": 487, "otherVariantsUntouched": 487, "gateBlocked": 487 }, "invalid_strength": { "injected": 487, "stopped": 487, "stoppedWithExpectedReason": 487, "classUnchangedWhereRequired": 487, "classCheckRequired": 487, "otherVariantsUntouched": 487, "gateBlocked": 487 }, "no_evidence_cited": { "injected": 462, "stopped": 462, "stoppedWithExpectedReason": 462, "otherVariantsUntouched": 462, "gateBlocked": 462 }, "predicate_failed": { "injected": 4208, "stopped": 4208, "stoppedWithExpectedReason": 4208, "classUnchangedWhereRequired": 4208, "classCheckRequired": 4208, "otherVariantsUntouched": 4208, "gateBlocked": 4208 }, "retired_criterion": { "injected": 487, "stopped": 487, "stoppedWithExpectedReason": 487, "classUnchangedWhereRequired": 487, "classCheckRequired": 487, "otherVariantsUntouched": 487, "gateBlocked": 487 }, "strength_exceeds_support": { "injected": 393, "stopped": 393, "stoppedWithExpectedReason": 393, "otherVariantsUntouched": 393, "gateBlocked": 393 }, "unknown_code": { "injected": 487, "stopped": 487, "stoppedWithExpectedReason": 487, "classUnchangedWhereRequired": 487, "classCheckRequired": 487, "otherVariantsUntouched": 487, "gateBlocked": 487 } }, "ledgerTampering": { "ledger_item_from_untrusted_agent:injected": 120, "ledger_item_from_untrusted_agent:rejected": 120, "ledger_value_edited:injected": 240, "ledger_value_edited:rejected": 240 } }, "languageModelCuration": { "model": "Claude Opus (Claude Code subagent, model alias opus)", "route": "agent runtime", "effort": "medium", "variants": 24, "strata": { "pathogenic null": 6, "pathogenic missense": 6, "uncertain": 6, "benign": 6 }, "requests": 4, "revisionRequests": 2, "refusals": 0, "tokens": {}, "listPriceUsd": null, "ledgerOnly": { "acceptedInExpertRecord": 31, "acceptedNotInExpertRecord": 8, "blockedInExpertRecord": 6, "blockedNotInExpertRecord": 1, "classificationMismatch": 3, "criteriaAccepted": 39, "criteriaBlocked": 7, "variants": 24, "blockedByReason": { "evidence_kind_missing": 7 }, "blockedByKind": { "citationIncompleteButSupported": 5, "citationIncompleteButSupportedInExpertRecord": 5, "ledgerContradictsClaim": 1, "ledgerContradictsClaimInExpertRecord": 1, "noSuchEvidenceInLedger": 1, "noSuchEvidenceInLedgerNotInExpertRecord": 1 }, "classification": { "auditedPathogenicWhereExpertIsNot": 0, "auditedSameAsExpert": 8, "auditedSameAsRuleEngine": 20, "claimedPathogenicWhereExpertIsNot": 0, "claimedSameAsExpert": 9 }, "blockedClaims": [ { "variant": "7-44153338-C-T", "stratum": "pathogenic missense", "claimed": "PP3_Strong", "reason": "evidence_kind_missing", "kind": "citationIncompleteButSupported", "inExpertRecord": true, "detail": "missing consequence" }, { "variant": "14-95107888-A-G", "stratum": "pathogenic missense", "claimed": "PP3_Moderate", "reason": "evidence_kind_missing", "kind": "citationIncompleteButSupported", "inExpertRecord": true, "detail": "missing consequence" }, { "variant": "7-44152420-C-T", "stratum": "pathogenic missense", "claimed": "PP3_Strong", "reason": "evidence_kind_missing", "kind": "citationIncompleteButSupported", "inExpertRecord": true, "detail": "missing consequence" }, { "variant": "7-44145614-G-T", "stratum": "pathogenic missense", "claimed": "PP3_Strong", "reason": "evidence_kind_missing", "kind": "citationIncompleteButSupported", "inExpertRecord": true, "detail": "missing consequence" }, { "variant": "9-34648376-G-A", "stratum": "pathogenic missense", "claimed": "PP3", "reason": "evidence_kind_missing", "kind": "citationIncompleteButSupported", "inExpertRecord": true, "detail": "missing consequence" }, { "variant": "11-108289759-T-C", "stratum": "pathogenic missense", "claimed": "PP3_Moderate", "reason": "evidence_kind_missing", "kind": "ledgerContradictsClaim", "inExpertRecord": true, "detail": "missing consequence" }, { "variant": "14-95117701-T-C", "stratum": "benign", "claimed": "BP1", "reason": "evidence_kind_missing", "kind": "noSuchEvidenceInLedger", "inExpertRecord": false, "detail": "missing truncating_only_gene" } ] }, "ledgerOnlyAfterOneRevision": { "acceptedInExpertRecord": 36, "acceptedNotInExpertRecord": 8, "blockedInExpertRecord": 1, "classificationMismatch": 1, "criteriaAccepted": 44, "criteriaBlocked": 1, "variants": 24, "blockedByReason": { "predicate_failed": 1 }, "blockedByKind": { "ledgerContradictsClaim": 1, "ledgerContradictsClaimInExpertRecord": 1 }, "classification": { "auditedPathogenicWhereExpertIsNot": 0, "auditedSameAsExpert": 10, "auditedSameAsRuleEngine": 23, "claimedPathogenicWhereExpertIsNot": 0, "claimedSameAsExpert": 9 }, "blockedClaims": [ { "variant": "11-108289759-T-C", "stratum": "pathogenic missense", "claimed": "PP3_Moderate", "reason": "predicate_failed", "kind": "ledgerContradictsClaim", "inExpertRecord": true, "detail": "no calibrated score reaches the PP3 threshold" } ] }, "recallAllowed": { "acceptedInExpertRecord": 28, "acceptedNotInExpertRecord": 2, "blockedInExpertRecord": 16, "blockedNotInExpertRecord": 7, "classificationMismatch": 8, "criteriaAccepted": 30, "criteriaBlocked": 23, "variants": 24, "blockedByReason": { "evidence_kind_missing": 19, "no_evidence_cited": 4 }, "blockedByKind": { "citationIncompleteButSupported": 12, "citationIncompleteButSupportedInExpertRecord": 8, "citationIncompleteButSupportedNotInExpertRecord": 4, "ledgerContradictsClaim": 2, "ledgerContradictsClaimInExpertRecord": 1, "ledgerContradictsClaimNotInExpertRecord": 1, "noSuchEvidenceInLedger": 9, "noSuchEvidenceInLedgerInExpertRecord": 7, "noSuchEvidenceInLedgerNotInExpertRecord": 2 }, "classification": { "auditedPathogenicWhereExpertIsNot": 0, "auditedSameAsExpert": 8, "auditedSameAsRuleEngine": 20, "claimedPathogenicWhereExpertIsNot": 0, "claimedSameAsExpert": 10 }, "blockedClaims": [ { "variant": "7-44153338-C-T", "stratum": "pathogenic missense", "claimed": "PS1_Moderate", "reason": "evidence_kind_missing", "kind": "citationIncompleteButSupported", "inExpertRecord": false, "detail": "missing consequence" }, { "variant": "7-44153338-C-T", "stratum": "pathogenic missense", "claimed": "PP3_Strong", "reason": "evidence_kind_missing", "kind": "citationIncompleteButSupported", "inExpertRecord": true, "detail": "missing consequence" }, { "variant": "14-95107888-A-G", "stratum": "pathogenic missense", "claimed": "PP3_Moderate", "reason": "evidence_kind_missing", "kind": "citationIncompleteButSupported", "inExpertRecord": true, "detail": "missing consequence" }, { "variant": "7-44152420-C-T", "stratum": "pathogenic missense", "claimed": "PS1", "reason": "evidence_kind_missing", "kind": "citationIncompleteButSupported", "inExpertRecord": false, "detail": "missing consequence" }, { "variant": "7-44152420-C-T", "stratum": "pathogenic missense", "claimed": "PP3_Strong", "reason": "evidence_kind_missing", "kind": "citationIncompleteButSupported", "inExpertRecord": true, "detail": "missing consequence" }, { "variant": "7-44145614-G-T", "stratum": "pathogenic missense", "claimed": "PM5", "reason": "evidence_kind_missing", "kind": "ledgerContradictsClaim", "inExpertRecord": false, "detail": "missing consequence" }, { "variant": "7-44145614-G-T", "stratum": "pathogenic missense", "claimed": "PP3_Strong", "reason": "evidence_kind_missing", "kind": "citationIncompleteButSupported", "inExpertRecord": true, "detail": "missing consequence" }, { "variant": "9-34648376-G-A", "stratum": "pathogenic missense", "claimed": "PP3", "reason": "evidence_kind_missing", "kind": "citationIncompleteButSupported", "inExpertRecord": true, "detail": "missing consequence" }, { "variant": "11-108289759-T-C", "stratum": "pathogenic missense", "claimed": "PP3_Moderate", "reason": "evidence_kind_missing", "kind": "ledgerContradictsClaim", "inExpertRecord": true, "detail": "missing consequence" }, { "variant": "21-34834610-G-A", "stratum": "uncertain", "claimed": "BP4", "reason": "evidence_kind_missing", "kind": "citationIncompleteButSupported", "inExpertRecord": true, "detail": "missing consequence" }, { "variant": "17-7221006-T-C", "stratum": "uncertain", "claimed": "PP3_Strong", "reason": "evidence_kind_missing", "kind": "citationIncompleteButSupported", "inExpertRecord": true, "detail": "missing consequence" }, { "variant": "10-14934424-A-T", "stratum": "uncertain", "claimed": "PP3_Moderate", "reason": "evidence_kind_missing", "kind": "citationIncompleteButSupported", "inExpertRecord": false, "detail": "missing consequence" }, { "variant": "21-34887005-G-T", "stratum": "uncertain", "claimed": "BP4", "reason": "no_evidence_cited", "kind": "noSuchEvidenceInLedger", "inExpertRecord": true, "detail": "BP4" }, { "variant": "21-34887005-G-T", "stratum": "uncertain", "claimed": "BP7", "reason": "evidence_kind_missing", "kind": "noSuchEvidenceInLedger", "inExpertRecord": false, "detail": "missing in_silico" }, { "variant": "21-34887059-G-C", "stratum": "uncertain", "claimed": "BP4", "reason": "no_evidence_cited", "kind": "noSuchEvidenceInLedger", "inExpertRecord": true, "detail": "BP4" }, { "variant": "21-34887059-G-C", "stratum": "uncertain", "claimed": "BP7", "reason": "evidence_kind_missing", "kind": "noSuchEvidenceInLedger", "inExpertRecord": false, "detail": "missing in_silico" }, { "variant": "21-34792270-G-A", "stratum": "benign", "claimed": "BP4", "reason": "no_evidence_cited", "kind": "noSuchEvidenceInLedger", "inExpertRecord": true, "detail": "BP4" }, { "variant": "21-34792270-G-A", "stratum": "benign", "claimed": "BP7", "reason": "evidence_kind_missing", "kind": "noSuchEvidenceInLedger", "inExpertRecord": true, "detail": "missing in_silico" }, { "variant": "10-87952202-C-T", "stratum": "benign", "claimed": "BP4", "reason": "evidence_kind_missing", "kind": "citationIncompleteButSupported", "inExpertRecord": true, "detail": "missing consequence" }, { "variant": "16-68737468-C-G", "stratum": "benign", "claimed": "BP4", "reason": "evidence_kind_missing", "kind": "citationIncompleteButSupported", "inExpertRecord": false, "detail": "missing consequence" }, { "variant": "21-34880600-A-C", "stratum": "benign", "claimed": "BP4", "reason": "no_evidence_cited", "kind": "noSuchEvidenceInLedger", "inExpertRecord": true, "detail": "BP4" }, { "variant": "21-34880600-A-C", "stratum": "benign", "claimed": "BP7", "reason": "evidence_kind_missing", "kind": "noSuchEvidenceInLedger", "inExpertRecord": true, "detail": "missing in_silico" }, { "variant": "21-34834616-A-AGGGAGGGGAG", "stratum": "benign", "claimed": "BP7", "reason": "evidence_kind_missing", "kind": "noSuchEvidenceInLedger", "inExpertRecord": true, "detail": "missing in_silico" } ] } }, "literatureEvidence": { "retrieval": { "development": { "variants": 24, "withPublicationsListed": 18, "withTextWindows": 17, "textWindows": 94 }, "heldOut": { "variants": 72, "withPublicationsListed": 43, "withTextWindows": 36, "textWindows": 270 } }, "verifierFaultInjection": { "injected": 493, "blocked": 493, "reachedLedger": 0, "byFault": { "finding_without_supporting_wording": { "injected": 154, "blocked": 154, "blockedWithExpectedReason": 154, "reachedLedger": 0 }, "homozygous_without_wording": { "injected": 27, "blocked": 27, "blockedWithExpectedReason": 27, "reachedLedger": 0 }, "invalid_direction": { "injected": 53, "blocked": 53, "blockedWithExpectedReason": 53, "reachedLedger": 0 }, "invented_window": { "injected": 53, "blocked": 53, "blockedWithExpectedReason": 53, "reachedLedger": 0 }, "no_window": { "injected": 53, "blocked": 53, "blockedWithExpectedReason": 53, "reachedLedger": 0 }, "second_allele_not_established": { "injected": 15, "blocked": 15, "blockedWithExpectedReason": 15, "reachedLedger": 0 }, "second_allele_not_in_window": { "injected": 32, "blocked": 32, "blockedWithExpectedReason": 32, "reachedLedger": 0 }, "unknown_kind": { "injected": 53, "blocked": 53, "blockedWithExpectedReason": 53, "reachedLedger": 0 }, "window_of_another_variant": { "injected": 53, "blocked": 53, "blockedWithExpectedReason": 53, "reachedLedger": 0 } } }, "reader": { "model": "Claude Sonnet (Claude Code subagent, model alias sonnet)", "route": "agent runtime", "requests": 8, "auditGateAfter": { "gate": "pass", "criteriaClaimed": 17526, "criteriaAccepted": 17526, "criteriaBlocked": 0, "blockedByReason": {}, "classificationMismatches": 0 } }, "secondReader": { "model": "azure/gpt-5.4-mini", "findingsRead": 28, "disagreed": 2, "runs": [ "6184a20f-c88f-43c1-a0be-40600bfe242b", "54f1de76-a71c-4326-84be-429f0c7e848e" ], "chargedUsd": 0.0188 }, "development": { "findingsProposed": 13, "findingsAccepted": 7, "findingsBlocked": 6, "blockedByReason": { "cue_missing": 5, "second_reader_disagrees": 1 }, "acceptedByKind": { "cosegregation": 1, "functional_assay": 3, "second_allele": 3 }, "againstExpertRecords": { "functional_assay": { "pipeline": 3, "expert": 7, "both": 2 }, "cosegregation": { "pipeline": 1, "expert": 5, "both": 1 }, "literature_second_allele": { "pipeline": 3, "expert": 10, "both": 3 } }, "acceptedForVariantsExpertsDidNotCallPathogenic": [], "byStratum": { "benign missense": { "variants": 4, "withAcceptedFinding": 0, "pathogenicOrLikelyBefore": 0, "pathogenicOrLikelyAfter": 0, "classChanged": 0 }, "pathogenic missense": { "variants": 12, "withAcceptedFinding": 6, "pathogenicOrLikelyBefore": 4, "pathogenicOrLikelyAfter": 4, "classChanged": 0 }, "pathogenic other": { "variants": 4, "withAcceptedFinding": 0, "pathogenicOrLikelyBefore": 0, "pathogenicOrLikelyAfter": 0, "classChanged": 0 }, "uncertain missense": { "variants": 4, "withAcceptedFinding": 0, "pathogenicOrLikelyBefore": 0, "pathogenicOrLikelyAfter": 0, "classChanged": 0 } }, "changes": [] }, "heldOut": { "findingsProposed": 27, "findingsAccepted": 19, "findingsBlocked": 8, "blockedByReason": { "cue_missing": 5, "other_allele_not_established": 2, "second_reader_disagrees": 1 }, "acceptedByKind": { "cosegregation": 3, "functional_assay": 10, "second_allele": 6 }, "againstExpertRecords": { "functional_assay": { "pipeline": 10, "expert": 21, "both": 4 }, "cosegregation": { "pipeline": 3, "expert": 17, "both": 2 }, "literature_second_allele": { "pipeline": 6, "expert": 15, "both": 4 } }, "acceptedForVariantsExpertsDidNotCallPathogenic": [ { "variant": "9-34647247-G-A", "stratum": "uncertain missense", "kind": "functional_assay", "direction": "pathogenic" }, { "variant": "2-202467547-A-C", "stratum": "benign missense", "kind": "functional_assay", "direction": "pathogenic" }, { "variant": "1-171652236-G-A", "stratum": "benign missense", "kind": "literature_second_allele", "direction": "pathogenic" } ], "byStratum": { "benign missense": { "variants": 12, "withAcceptedFinding": 2, "pathogenicOrLikelyBefore": 0, "pathogenicOrLikelyAfter": 0, "classChanged": 0 }, "pathogenic missense": { "variants": 36, "withAcceptedFinding": 12, "pathogenicOrLikelyBefore": 16, "pathogenicOrLikelyAfter": 18, "classChanged": 2 }, "pathogenic other": { "variants": 12, "withAcceptedFinding": 1, "pathogenicOrLikelyBefore": 0, "pathogenicOrLikelyAfter": 0, "classChanged": 0 }, "uncertain missense": { "variants": 12, "withAcceptedFinding": 1, "pathogenicOrLikelyBefore": 0, "pathogenicOrLikelyAfter": 0, "classChanged": 0 } }, "changes": [ { "variant": "X-38317418-C-G", "stratum": "pathogenic missense", "expert": "Likely pathogenic", "before": "Uncertain significance", "after": "Likely pathogenic", "applied": [ "PS3_Supporting", "PM2_Supporting", "PP3_Strong" ] }, { "variant": "1-171636287-C-T", "stratum": "pathogenic missense", "expert": "Likely pathogenic", "before": "Uncertain significance", "after": "Likely pathogenic", "applied": [ "PM2_Supporting", "PP1", "PP3_Strong" ] } ] }, "variantsOutsideSampleChanged": 0 } }