{ "data": [ { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://erepo.genome.network/evrepo/api/summary/classification/1436fa1b-2178-480a-9711-337815571f93/doc/sepio/version/1.0.0", "assertionMethod": { "type": "VariantPathogenicityInterpretationGuideline" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0007783", "id": "MONDO:0007783", "label": "malignant hyperthermia, susceptibility to, 1", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA024747/MONDO:0007783/012/el/0/1804", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA024747/MONDO:0007783/012/ei/1/1805", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50038_EP161901766675837", "id": "CG-PCER-AGENT:CG_50038_EP161901766675837", "type": "Agent" }, "contributionDate": { "date": "2022/7/11", "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/CA024747/MONDO:0007783/012/el/0/1804/1806", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA024747/MONDO:0007783/012/ci/CA024747/MONDO:0007783/012.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50038_EP161901766675837", "id": "CG-PCER-AGENT:CG_50038_EP161901766675837", "type": "Agent" }, "contributionDate": { "date": "2022/7/11", "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": "CA024747/MONDO:0007783/012/ci/CA024747/MONDO:0007783/012.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA024747/MONDO:0007783/012/0/1804/1806", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA024747/MONDO:0007783/012/1/1805", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA024747/MONDO:0007783/012/0/1804", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA024747/MONDO:0007783/012/el/0/1702", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA024747/MONDO:0007783/012/ei/1/1703", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50038_EP161901766675837", "id": "CG-PCER-AGENT:CG_50038_EP161901766675837", "type": "Agent" }, "contributionDate": { "date": "2022/7/11", "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/0069", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000328", "id": "SEPIO:0000328", "label": "Benign Strong" }, "id": "0069", "label": "BS2", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA024747/MONDO:0007783/012/el/0/1702/1704", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA024747/MONDO:0007783/012/ci/CA024747/MONDO:0007783/012.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50038_EP161901766675837", "id": "CG-PCER-AGENT:CG_50038_EP161901766675837", "type": "Agent" }, "comments": "This variant has been identified in six individuals with negative IVCT/CHCT results, BS2 (PMID:30236257). 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", "contributionDate": { "date": "2022/7/11", "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": "CA024747/MONDO:0007783/012/ci/CA024747/MONDO:0007783/012.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA024747/MONDO:0007783/012/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA024747/MONDO:0007783/012/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA024747/MONDO:0007783/012/0/1828", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA024747/MONDO:0007783/012/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA024747/MONDO:0007783/012/ei/1/1736", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50038_EP161901766675837", "id": "CG-PCER-AGENT:CG_50038_EP161901766675837", "type": "Agent" }, "contributionDate": { "date": "2022/7/11", "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/CA024747/MONDO:0007783/012/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA024747/MONDO:0007783/012/ci/CA024747/MONDO:0007783/012.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50038_EP161901766675837", "id": "CG-PCER-AGENT:CG_50038_EP161901766675837", "type": "Agent" }, "comments": "This variant has been reported in 178 unrelated individuals who have a personal or family history of a malignant hyperthermia reaction, 174 of these individuals had a positive in vitro contracture test (IVCT) or caffeine halothane contracture test (CHCT) result (if the proband was unavailable for testing, a positive diagnostic test result in a mutation-positive relative was counted, PS4 (PMID: 30236257, 10484775, 23558838, 16163667, 21455645, 23842196, 7849712, 7881417, 11575529, 15731587, 11668625, 12059893, 12151923, 31559918, 10700782, 17081125, 18564801, 20681998, 21965348, 23460944, 25735680, 25960145, 9030597, 25268394, 17667681). ", "contributionDate": { "date": "2022/7/11", "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": "CA024747/MONDO:0007783/012/ci/CA024747/MONDO:0007783/012.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA024747/MONDO:0007783/012/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA024747/MONDO:0007783/012/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA024747/MONDO:0007783/012/0/1735", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA024747/MONDO:0007783/012/el/0/1648", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA024747/MONDO:0007783/012/ei/1/1649", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50038_EP161901766675837", "id": "CG-PCER-AGENT:CG_50038_EP161901766675837", "type": "Agent" }, "contributionDate": { "date": "2022/7/11", "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/0023", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0023", "label": "PP1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA024747/MONDO:0007783/012/el/0/1648/1650", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA024747/MONDO:0007783/012/ci/CA024747/MONDO:0007783/012.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50038_EP161901766675837", "id": "CG-PCER-AGENT:CG_50038_EP161901766675837", "type": "Agent" }, "comments": "This variant segregates with MHS in at least 20 individuals, PP1_Strong (PMID: 7849712, 11575529, 12059893, 25960145).", "contributionDate": { "date": "2022/7/11", "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": "CA024747/MONDO:0007783/012/ci/CA024747/MONDO:0007783/012.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA024747/MONDO:0007783/012/0/1648/1650", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA024747/MONDO:0007783/012/1/1649", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA024747/MONDO:0007783/012/0/1648", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA024747/MONDO:0007783/012/el/0/1690", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA024747/MONDO:0007783/012/ei/1/1691", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50038_EP161901766675837", "id": "CG-PCER-AGENT:CG_50038_EP161901766675837", "type": "Agent" }, "contributionDate": { "date": "2022/7/11", "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/0025", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "0025", "label": "PP3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA024747/MONDO:0007783/012/el/0/1690/1692", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA024747/MONDO:0007783/012/ci/CA024747/MONDO:0007783/012.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50038_EP161901766675837", "id": "CG-PCER-AGENT:CG_50038_EP161901766675837", "type": "Agent" }, "comments": "A REVEL score >0.85 (0.956) supports a pathogenic status for this variant, PP3_Moderate. ", "contributionDate": { "date": "2022/7/11", "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": "CA024747/MONDO:0007783/012/ci/CA024747/MONDO:0007783/012.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA024747/MONDO:0007783/012/0/1690/1692", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA024747/MONDO:0007783/012/1/1691", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA024747/MONDO:0007783/012/0/1690", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA024747/MONDO:0007783/012/el/0/1615", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA024747/MONDO:0007783/012/ei/1/1616", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50038_EP161901766675837", "id": "CG-PCER-AGENT:CG_50038_EP161901766675837", "type": "Agent" }, "contributionDate": { "date": "2022/7/11", "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/006", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "006", "label": "PM1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA024747/MONDO:0007783/012/el/0/1615/1617", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA024747/MONDO:0007783/012/ci/CA024747/MONDO:0007783/012.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50038_EP161901766675837", "id": "CG-PCER-AGENT:CG_50038_EP161901766675837", "type": "Agent" }, "comments": "This variant resides in a region of RYR1 considered to be a hotspot for pathogenic variants that contribute to MHS, PM1 (PMID: 21118704).", "contributionDate": { "date": "2022/7/11", "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": "CA024747/MONDO:0007783/012/ci/CA024747/MONDO:0007783/012.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA024747/MONDO:0007783/012/0/1615/1617", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA024747/MONDO:0007783/012/1/1616", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA024747/MONDO:0007783/012/0/1615", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA024747/MONDO:0007783/012", "metadata": { "created": "2024-09-28T00:11:01.158Z", "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 00:11:01 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA6668-3", "id": "LN:LA6668-3", "label": "Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "1436fa1b-2178-480a-9711-337815571f93", "variant": { "@id": "https://reg.genome.network/allele/CA024747", "id": "CAR:CA024747", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000540.3:c.7300G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000540.3(RYR1):c.7300G>A (p.Gly2434Arg)" } ], "type": "CAR" } } ], "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-04-04T15:05:01.189Z" } }, "status": { "code": 200, "name": "OK" } }