{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://erepo.genome.network/evrepo/api/summary/classification/76f96ea3-4750-4169-9a00-f6e11ea64943/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1535826188", "label": "ClinGen Cardiomyopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for TNNT2 Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0005045", "id": "MONDO:0005045", "label": "hypertrophic cardiomyopathy", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA005312/MONDO:0005045/099/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA005312/MONDO:0005045/099/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50002_EP155190197442076", "id": "CG-PCER-AGENT:CG_50002_EP155190197442076", "type": "Agent" }, "contributionDate": { "date": "2025/11/14", "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/CA005312/MONDO:0005045/099/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA005312/MONDO:0005045/099/ci/CA005312/MONDO:0005045/099.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50002_EP155190197442076", "id": "CG-PCER-AGENT:CG_50002_EP155190197442076", "type": "Agent" }, "comments": "\ngnomad 2.1 Latino\t1\t33806 Upper 95% CI: 0.01% PM2 not met \ngnomad 2.1 total 1/242296 Upper 95% CI 0.002% Pm2 Met\n\ngnomad 4.1 : Admixed American\t1\t59510\tUpper 95% CI: 0.008% PM2 not met\nNon-Finnish European\t5\t1178844 Upper 95% CI: 0.009% PM2 not met\nNon-Finnish European\t5\t1178844", "contributionDate": { "date": "2025/11/14", "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": "CA005312/MONDO:0005045/099/ci/CA005312/MONDO:0005045/099.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA005312/MONDO:0005045/099/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA005312/MONDO:0005045/099/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA005312/MONDO:0005045/099/0/1636", "type": "EvidenceLine" }, { "@id": 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"CG-PCER-VARINT:CA005312/MONDO:0005045/099/0/1594", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA005312/MONDO:0005045/099/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA005312/MONDO:0005045/099/ei/1/1829", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50002_EP155190197442076", "id": "CG-PCER-AGENT:CG_50002_EP155190197442076", "type": "Agent" }, "contributionDate": { "date": "2025/11/14", "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/CA005312/MONDO:0005045/099/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA005312/MONDO:0005045/099/ci/CA005312/MONDO:0005045/099.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50002_EP155190197442076", "id": "CG-PCER-AGENT:CG_50002_EP155190197442076", "type": "Agent" }, "comments": "none", "contributionDate": { "date": "2025/11/14", "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": "CA005312/MONDO:0005045/099/ci/CA005312/MONDO:0005045/099.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA005312/MONDO:0005045/099/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA005312/MONDO:0005045/099/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA005312/MONDO:0005045/099/0/1828", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA005312/MONDO:0005045/099/el/0/1699", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA005312/MONDO:0005045/099/ei/1/1700", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50002_EP155190197442076", "id": "CG-PCER-AGENT:CG_50002_EP155190197442076", "type": "Agent" }, "contributionDate": { "date": "2025/11/14", "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/CA005312/MONDO:0005045/099/el/0/1699/1701", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA005312/MONDO:0005045/099/ci/CA005312/MONDO:0005045/099.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50002_EP155190197442076", "id": "CG-PCER-AGENT:CG_50002_EP155190197442076", "type": "Agent" }, "comments": "This variant has been reported in individuals with HCM (LMM data, Richard 2003 PMID: 12707239, Gandjbakhch 2010 PMID: 25575096, Brito 2012 PMID: 22857948, Lopes 2013 PMID: 23396983, Bales 2016 PMID: 26936621, Walsh 2017 PMID: 27532257, Mademont-Soler 2017 PMID: 28771489, Ho 2018 PMID: 30297972) and has been identified in been identified in 1 out of 242296 (0.002% FAF 95% CI) of global pan-ethnic chromosomes in gnomAD (https://gnomad.broadinstitute.org/; v.2.1). This variant is statistically increased in individuals with HCM compared to controls [OR lower 95% CI >10]. Therefore, PS4_Moderate criteria has been applied and the PM2_Supporting criterion has been applied (PM2_Supporting). \n", "contributionDate": { "date": "2025/11/14", "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": "CA005312/MONDO:0005045/099/ci/CA005312/MONDO:0005045/099.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA005312/MONDO:0005045/099/0/1699/1701", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA005312/MONDO:0005045/099/1/1700", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA005312/MONDO:0005045/099/0/1699", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA005312/MONDO:0005045/099/el/0/1648", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA005312/MONDO:0005045/099/ei/1/1649", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50002_EP155190197442076", "id": "CG-PCER-AGENT:CG_50002_EP155190197442076", "type": "Agent" }, "contributionDate": { "date": "2025/11/14", "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/CA005312/MONDO:0005045/099/el/0/1648/1650", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA005312/MONDO:0005045/099/ci/CA005312/MONDO:0005045/099.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50002_EP155190197442076", "id": "CG-PCER-AGENT:CG_50002_EP155190197442076", "type": "Agent" }, "comments": "This variant segregated with disease in 7 affected relatives from 6 families (Richard 2003 PMID: 12707239, Gandjbakhch 2010 PMID: 20439259, Brito 2012 PMID: 22857948, D. Brito pers comm, GeneDx pers comm; LMM data)\t\t", "contributionDate": { "date": "2025/11/14", "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": "CA005312/MONDO:0005045/099/ci/CA005312/MONDO:0005045/099.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA005312/MONDO:0005045/099/0/1648/1650", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA005312/MONDO:0005045/099/1/1649", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA005312/MONDO:0005045/099/0/1648", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA005312/MONDO:0005045/099/el/0/1588", "evidenceItem": [ { "@id": 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"none", "contributionDate": { "date": "2025/11/14", "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": "CA005312/MONDO:0005045/099/ci/CA005312/MONDO:0005045/099.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA005312/MONDO:0005045/099/0/1588/1590", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA005312/MONDO:0005045/099/1/1589", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA005312/MONDO:0005045/099/0/1588", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA005312/MONDO:0005045/099/el/0/1591", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA005312/MONDO:0005045/099/ei/1/1592", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50002_EP155190197442076", "id": "CG-PCER-AGENT:CG_50002_EP155190197442076", "type": "Agent" }, "contributionDate": { "date": "2025/11/14", "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/CA005312/MONDO:0005045/099/el/0/1591/1593", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA005312/MONDO:0005045/099/ci/CA005312/MONDO:0005045/099.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50002_EP155190197442076", "id": "CG-PCER-AGENT:CG_50002_EP155190197442076", "type": "Agent" }, "comments": "2 aa deleted", "contributionDate": { "date": "2025/11/14", "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": "CA005312/MONDO:0005045/099/ci/CA005312/MONDO:0005045/099.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA005312/MONDO:0005045/099/0/1591/1593", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA005312/MONDO:0005045/099/1/1592", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA005312/MONDO:0005045/099/0/1591", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA005312/MONDO:0005045/099", "metadata": { "created": "2025-11-14T19:08:10.327Z", "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, 14 Nov 2025 19:08:10 -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": "76f96ea3-4750-4169-9a00-f6e11ea64943", "variant": { "@id": "https://reg.genome.network/allele/CA005312", "id": "CAR:CA005312", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_001276345.2:c.890G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_001276345.2(TNNT2):c.890G>A (p.Trp297Ter)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-06-08T02:15:24.592Z" } }, "status": { "code": 200, "name": "OK" } }