{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/588c71a8-9a58-4904-8a95-4da3714631e8/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1528339111", "label": "ClinGen Monogenic Diabetes Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for GCK Version 3.1.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "3.1.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0015967", "id": "MONDO:0015967", "label": "monogenic diabetes", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367403826/MONDO:0015967/086/el/0/1615", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367403826/MONDO:0015967/086/ei/1/1616", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "contributionDate": { "date": "2026/2/26", "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/CA367403826/MONDO:0015967/086/el/0/1615/1617", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA367403826/MONDO:0015967/086/ci/CA367403826/MONDO:0015967/086.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "contributionDate": { "date": "2026/2/26", "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": "CA367403826/MONDO:0015967/086/ci/CA367403826/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA367403826/MONDO:0015967/086/0/1615/1617", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA367403826/MONDO:0015967/086/1/1616", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA367403826/MONDO:0015967/086/0/1615", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367403826/MONDO:0015967/086/el/0/1678", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367403826/MONDO:0015967/086/ei/1/1679", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "contributionDate": { "date": "2026/2/26", "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/CA367403826/MONDO:0015967/086/el/0/1678/1680", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA367403826/MONDO:0015967/086/ci/CA367403826/MONDO:0015967/086.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "comments": "This variant segregated with hyperglycemia, with two informative meioses in two families (PP1; PMID: 25665835, internal lab contributors). 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"comments": "GCK is defined by the ClinGen MDEP as a gene that has a low rate of benign missense variation and has pathogenic missense variants as a common mechanism of disease (PP2).", "contributionDate": { "date": "2026/2/26", "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": "CA367403826/MONDO:0015967/086/ci/CA367403826/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA367403826/MONDO:0015967/086/0/1837/1839", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA367403826/MONDO:0015967/086/1/1838", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA367403826/MONDO:0015967/086/0/1837", "type": "EvidenceLine" }, { "@id": 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"EvidenceLine" } ], "id": "CG-PCER-VARINT:CA367403826/MONDO:0015967/086/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA367403826/MONDO:0015967/086/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367403826/MONDO:0015967/086/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367403826/MONDO:0015967/086/ei/1/1829", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "contributionDate": { "date": "2026/2/26", "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/CA367403826/MONDO:0015967/086/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA367403826/MONDO:0015967/086/ci/CA367403826/MONDO:0015967/086.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "comments": "The relative activity index (RAI) of this variant was above the MDEP cutoff of 0.5 and a relative stability index was not calculated (PMID: 25665835). ", "contributionDate": { "date": "2026/2/26", "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": "CA367403826/MONDO:0015967/086/ci/CA367403826/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA367403826/MONDO:0015967/086/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA367403826/MONDO:0015967/086/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA367403826/MONDO:0015967/086/0/1828", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367403826/MONDO:0015967/086/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367403826/MONDO:0015967/086/ei/1/1736", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "contributionDate": { "date": "2026/2/26", "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/CA367403826/MONDO:0015967/086/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA367403826/MONDO:0015967/086/ci/CA367403826/MONDO:0015967/086.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "comments": "This variant was identified in 7 unrelated individuals with hyperglycemia (PS4; PMID: 25665835, 33852230, 17573900, internal lab contributors). ", "contributionDate": { "date": "2026/2/26", "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": "CA367403826/MONDO:0015967/086/ci/CA367403826/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA367403826/MONDO:0015967/086/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA367403826/MONDO:0015967/086/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA367403826/MONDO:0015967/086/0/1735", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367403826/MONDO:0015967/086/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367403826/MONDO:0015967/086/ei/1/1832", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "contributionDate": { "date": "2026/2/26", "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/CA367403826/MONDO:0015967/086/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA367403826/MONDO:0015967/086/ci/CA367403826/MONDO:0015967/086.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "comments": "This variant was identified in an individual with a clinical history highly specific for GCK-hyperglycemia (fasting glucose 5.5-8 mmol/L and HbA1c 5.6 - 7.6% and negative antibody) (PP4_Moderate; internal lab contributors). ", "contributionDate": { "date": "2026/2/26", "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": "CA367403826/MONDO:0015967/086/ci/CA367403826/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA367403826/MONDO:0015967/086/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA367403826/MONDO:0015967/086/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA367403826/MONDO:0015967/086/0/1831", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367403826/MONDO:0015967/086/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA367403826/MONDO:0015967/086/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "contributionDate": { "date": "2026/2/26", "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/CA367403826/MONDO:0015967/086/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA367403826/MONDO:0015967/086/ci/CA367403826/MONDO:0015967/086.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50016_EP163553328993009", "id": "CG-PCER-AGENT:CG_50016_EP163553328993009", "type": "Agent" }, "comments": "This variant has an incomputable gnomAD v4.1.0 Grpmax filtering allele frequency due to no more than one copy in any subpopulation, thereby meeting the ClinGen MDEP threshold criteria for PM2_Supporting (Grpmax FAF <= 0.000003) (PM2_Supporting). ", "contributionDate": { "date": "2026/2/26", "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": "CA367403826/MONDO:0015967/086/ci/CA367403826/MONDO:0015967/086.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA367403826/MONDO:0015967/086/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA367403826/MONDO:0015967/086/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA367403826/MONDO:0015967/086/0/1636", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA367403826/MONDO:0015967/086", "metadata": { "created": "2026-02-26T16:06:37.336Z", "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": "Thu, 26 Feb 2026 16:06:37 -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": "588c71a8-9a58-4904-8a95-4da3714631e8", "variant": { "@id": "https://reg.genome.network/allele/CA367403826", "id": "CAR:CA367403826", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000162.5:c.56T>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000162.5(GCK):c.56T>A (p.Ile19Asn)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-01T07:47:31.472Z" } }, "status": { "code": 200, "name": "OK" } }