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Based on this evidence, this variant scores 5.5 total points meeting the TP53 VCEP phenotype scoring criteria of 4-7.5 points. (PS4; PMIDs: 1581912, 27866339, 28486781, 27501770, Internal contributors).", "contributionDate": { "date": "2025/12/5", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA000257/MONDO:0018875/009/ci/CA000257/MONDO:0018875/009.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA000257/MONDO:0018875/009/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA000257/MONDO:0018875/009/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA000257/MONDO:0018875/009/0/1735", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA000257/MONDO:0018875/009/el/0/1681", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA000257/MONDO:0018875/009/ei/1/1682", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50013_EP157989641412139", "id": "CG-PCER-AGENT:CG_50013_EP157989641412139", "type": "Agent" }, "contributionDate": { "date": "2025/12/5", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA000257/MONDO:0018875/009/el/0/1681/1683", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA000257/MONDO:0018875/009/ci/CA000257/MONDO:0018875/009.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50013_EP157989641412139", "id": "CG-PCER-AGENT:CG_50013_EP157989641412139", "type": "Agent" }, "comments": "This variant has 9 somatic occurrences for the same amino acid change in cancerhotspots.org (v2) sufficient to be defined as a mutational hotspot by the Clingen TP53 VCEP (2-9 somatic occurrences, PMID: 30311369) (PM1_Supporting).", "contributionDate": { "date": "2025/12/5", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA000257/MONDO:0018875/009/ci/CA000257/MONDO:0018875/009.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA000257/MONDO:0018875/009/0/1681/1683", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA000257/MONDO:0018875/009/1/1682", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA000257/MONDO:0018875/009/0/1681", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA000257/MONDO:0018875/009/el/0/1690", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA000257/MONDO:0018875/009/ei/1/1691", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50013_EP157989641412139", "id": "CG-PCER-AGENT:CG_50013_EP157989641412139", "type": "Agent" }, "contributionDate": { "date": "2025/12/5", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA000257/MONDO:0018875/009/el/0/1690/1692", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA000257/MONDO:0018875/009/ci/CA000257/MONDO:0018875/009.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50013_EP157989641412139", "id": "CG-PCER-AGENT:CG_50013_EP157989641412139", "type": "Agent" }, "comments": "Computational predictor scores (BayesDel = 0.4693; Align GVGD = Class C65) are above recommended thresholds (BayesDel > 0.16 and an Align GVGD Class of 65), evidence that correlates with impact to TP53 via protein change (PP3_Moderate).", "contributionDate": { "date": "2025/12/5", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA000257/MONDO:0018875/009/ci/CA000257/MONDO:0018875/009.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA000257/MONDO:0018875/009/0/1690/1692", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA000257/MONDO:0018875/009/1/1691", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA000257/MONDO:0018875/009/0/1690", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA000257/MONDO:0018875/009/el/0/1804", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA000257/MONDO:0018875/009/ei/1/1805", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50013_EP157989641412139", "id": "CG-PCER-AGENT:CG_50013_EP157989641412139", "type": "Agent" }, "contributionDate": { "date": "2025/12/5", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA000257/MONDO:0018875/009/el/0/1804/1806", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA000257/MONDO:0018875/009/ci/CA000257/MONDO:0018875/009.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50013_EP157989641412139", "id": "CG-PCER-AGENT:CG_50013_EP157989641412139", "type": "Agent" }, "contributionDate": { "date": "2025/12/5", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA000257/MONDO:0018875/009/ci/CA000257/MONDO:0018875/009.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA000257/MONDO:0018875/009/0/1804/1806", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA000257/MONDO:0018875/009/1/1805", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA000257/MONDO:0018875/009/0/1804", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA000257/MONDO:0018875/009/el/0/1588", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA000257/MONDO:0018875/009/ei/1/1589", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50013_EP157989641412139", "id": "CG-PCER-AGENT:CG_50013_EP157989641412139", "type": "Agent" }, "contributionDate": { "date": "2025/12/5", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA000257/MONDO:0018875/009/el/0/1588/1590", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA000257/MONDO:0018875/009/ci/CA000257/MONDO:0018875/009.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50013_EP157989641412139", "id": "CG-PCER-AGENT:CG_50013_EP157989641412139", "type": "Agent" }, "comments": "In vitro assays performed in yeast and/or human cell lines showed partially functional transactivation and retained growth suppression activity suggesting that this variant does not impact protein function; however, all assays did not agree (BS3_Supporting not met; PMIDs: 12826609, 30224644, 29979965, 39774325).", "contributionDate": { "date": "2025/12/5", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA000257/MONDO:0018875/009/ci/CA000257/MONDO:0018875/009.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA000257/MONDO:0018875/009/0/1588/1590", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA000257/MONDO:0018875/009/1/1589", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA000257/MONDO:0018875/009/0/1588", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA000257/MONDO:0018875/009/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA000257/MONDO:0018875/009/ei/1/1832", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50013_EP157989641412139", "id": "CG-PCER-AGENT:CG_50013_EP157989641412139", "type": "Agent" }, "contributionDate": { "date": "2025/12/5", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA000257/MONDO:0018875/009/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA000257/MONDO:0018875/009/ci/CA000257/MONDO:0018875/009.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50013_EP157989641412139", "id": "CG-PCER-AGENT:CG_50013_EP157989641412139", "type": "Agent" }, "comments": "At least two individuals with this variant were found to have a variant allele fraction of 5-25%, which is a significant predictor of variant pathogenicity (PP4_Moderate, PMID: 34906512, Internal lab contributor).", "contributionDate": { "date": "2025/12/5", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "id": "CA000257/MONDO:0018875/009/ci/CA000257/MONDO:0018875/009.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA000257/MONDO:0018875/009/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA000257/MONDO:0018875/009/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA000257/MONDO:0018875/009/0/1831", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA000257/MONDO:0018875/009", "metadata": { "created": "2025-12-05T15:15:43.654Z", "note": "DISCLAIMER: While the data/content in this document is approved by ClinGen expert panel(s), the SEPIO schema presented here is an initial prototype and has not been reviewed nor finalized by the ClinGen Data Exchange Modeling Team. We expect it to differ significantly from the final schema.", "producedAtUTC": "Fri, 05 Dec 2025 15:15:43 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "299d149c-670b-4c03-b78c-1368a1e93d27", "variant": { "@id": "https://reg.genome.network/allele/CA000257", "id": "CAR:CA000257", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000546.6:c.541C>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000546.6(TP53):c.541C>T (p.Arg181Cys)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-05-05T15:42:28.863Z" } }, "status": { "code": 200, "name": "OK" } }