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which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0051", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0051", "label": "PS2", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397842518/MONDO:0018875/009/el/0/1663/1665", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA397842518/MONDO:0018875/009/ci/CA397842518/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 been identified as a de novo occurrence with confirmed parental relationships in 1 individual and as a de novo occurrence with unconfirmed parental relationships in 1 individual with an LFS-associated cancer totaling 6 phenotype points (PS2; PMID: 19701813, 25318593). ", "contributionDate": { "date": "2024/8/5", "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": "CA397842518/MONDO:0018875/009/ci/CA397842518/MONDO:0018875/009.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA397842518/MONDO:0018875/009/0/1663/1665", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA397842518/MONDO:0018875/009/1/1664", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA397842518/MONDO:0018875/009/0/1663", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397842518/MONDO:0018875/009/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397842518/MONDO:0018875/009/ei/1/1829", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50013_EP157989641412139", "id": "CG-PCER-AGENT:CG_50013_EP157989641412139", "type": "Agent" }, "contributionDate": { "date": "2024/8/5", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0052", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0052", "label": "PS3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397842518/MONDO:0018875/009/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA397842518/MONDO:0018875/009/ci/CA397842518/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 non-functional transactivation and loss of growth suppression activity indicating that this variant impacts protein function (PS3; PMIDs: 12826609, 30224644, 29979965).", "contributionDate": { "date": "2024/8/5", "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": "CA397842518/MONDO:0018875/009/ci/CA397842518/MONDO:0018875/009.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA397842518/MONDO:0018875/009/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA397842518/MONDO:0018875/009/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA397842518/MONDO:0018875/009/0/1828", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397842518/MONDO:0018875/009/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397842518/MONDO:0018875/009/ei/1/1736", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50013_EP157989641412139", "id": "CG-PCER-AGENT:CG_50013_EP157989641412139", "type": "Agent" }, "contributionDate": { "date": "2024/8/5", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0053", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0053", "label": "PS4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397842518/MONDO:0018875/009/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA397842518/MONDO:0018875/009/ci/CA397842518/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 received a total of 1 point across 2 unrelated probands. However, PS4 cannot be applied because these were both de novo cases counted towards PS2. (PS4 not met; PMIDs: 29070607, 19701813).", "contributionDate": { "date": "2024/8/5", "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": "CA397842518/MONDO:0018875/009/ci/CA397842518/MONDO:0018875/009.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA397842518/MONDO:0018875/009/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA397842518/MONDO:0018875/009/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA397842518/MONDO:0018875/009/0/1735", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397842518/MONDO:0018875/009/el/0/1681", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397842518/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": "2024/8/5", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0054", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0054", "label": "PM1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397842518/MONDO:0018875/009/el/0/1681/1683", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA397842518/MONDO:0018875/009/ci/CA397842518/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 7 somatic occurrences for the same amino acid change in cancerhotspots.org (v2) sufficient to be defined as a mutational hotspotcritical functional domain by the Clingen TP53 VCEP (2-9 somatic occurrences, PMID: 30311369) (PM1_Supporting).", "contributionDate": { "date": "2024/8/5", "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": "CA397842518/MONDO:0018875/009/ci/CA397842518/MONDO:0018875/009.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA397842518/MONDO:0018875/009/0/1681/1683", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA397842518/MONDO:0018875/009/1/1682", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA397842518/MONDO:0018875/009/0/1681", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397842518/MONDO:0018875/009/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397842518/MONDO:0018875/009/ei/1/1781", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50013_EP157989641412139", "id": "CG-PCER-AGENT:CG_50013_EP157989641412139", "type": "Agent" }, "contributionDate": { "date": "2024/8/5", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/008", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "008", "label": "PM5", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397842518/MONDO:0018875/009/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA397842518/MONDO:0018875/009/ci/CA397842518/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": "3 different missense variants (c.427G>A; p.Val143Met and c.427G>T; p.Val143Leu and c.428T>G; p.Val143Gly) in the same codon have been reported in ClinVar (Variation ID: 185729, 486556 and 486556). However, these variants have not yet met the criteria to be classified as pathogenic or likely pathogenic by the ClinGen TP53 VCEP’s specifications (PM5 not met).", "contributionDate": { "date": "2024/8/5", "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": "CA397842518/MONDO:0018875/009/ci/CA397842518/MONDO:0018875/009.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA397842518/MONDO:0018875/009/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA397842518/MONDO:0018875/009/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA397842518/MONDO:0018875/009/0/1780", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397842518/MONDO:0018875/009/el/0/1804", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397842518/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": "2024/8/5", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0070", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000328", "id": "SEPIO:0000328", "label": "Benign Strong" }, "id": "0070", "label": "BS1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397842518/MONDO:0018875/009/el/0/1804/1806", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA397842518/MONDO:0018875/009/ci/CA397842518/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": "2024/8/5", "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": "CA397842518/MONDO:0018875/009/ci/CA397842518/MONDO:0018875/009.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA397842518/MONDO:0018875/009/0/1804/1806", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA397842518/MONDO:0018875/009/1/1805", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA397842518/MONDO:0018875/009/0/1804", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397842518/MONDO:0018875/009/el/0/1588", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397842518/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": "2024/8/5", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0072", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000328", "id": "SEPIO:0000328", "label": "Benign Strong" }, "id": "0072", "label": "BS3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA397842518/MONDO:0018875/009/el/0/1588/1590", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA397842518/MONDO:0018875/009/ci/CA397842518/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": "2024/8/5", "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": "CA397842518/MONDO:0018875/009/ci/CA397842518/MONDO:0018875/009.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA397842518/MONDO:0018875/009/0/1588/1590", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA397842518/MONDO:0018875/009/1/1589", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA397842518/MONDO:0018875/009/0/1588", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA397842518/MONDO:0018875/009", "metadata": { "created": "2024-09-28T05:21:36.515Z", "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": "Sat, 28 Sep 2024 05:21:36 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "2.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA6668-3", "id": "LN:LA6668-3", "label": "Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "96976462-a14e-41e1-9dc6-73aa6108c844", "variant": { "@id": "https://reg.genome.network/allele/CA397842518", "id": "CAR:CA397842518", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_001276761.1:c.311T>C" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_001276761.1:c.311T>C" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-08-04T15:09:12.795Z" } }, "status": { "code": 200, "name": "OK" } }