{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/b02e5129-d33a-4445-ab99-aa3dd8fc3d6d/doc/sepio/version/2.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/635003679", "label": "ClinGen Glaucoma Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MYOC Version 2.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "2.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0005338", "id": "MONDO:0005338", "label": "open-angle glaucoma", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/el/0/1684", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/ei/1/1685", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2026/1/20", "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/CA343724569/MONDO:0005338/019/el/0/1684/1686", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA343724569/MONDO:0005338/019/ci/CA343724569/MONDO:0005338/019.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "This criterion was not met as PP3 has been met.", "contributionDate": { "date": "2026/1/20", "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": "CA343724569/MONDO:0005338/019/ci/CA343724569/MONDO:0005338/019.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1684/1686", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/1/1685", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1684", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/el/0/1777", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/ei/1/1778", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2026/1/20", "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/CA343724569/MONDO:0005338/019/el/0/1777/1779", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA343724569/MONDO:0005338/019/ci/CA343724569/MONDO:0005338/019.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "This criterion was not met as PM2_Supporting has been met.", "contributionDate": { "date": "2026/1/20", "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": "CA343724569/MONDO:0005338/019/ci/CA343724569/MONDO:0005338/019.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1777/1779", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/1/1778", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1777", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/el/0/1765", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/ei/1/1766", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2026/1/20", "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/CA343724569/MONDO:0005338/019/el/0/1765/1767", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA343724569/MONDO:0005338/019/ci/CA343724569/MONDO:0005338/019.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "An established LP or P variant causing this same amino acid change has not been identified.", "contributionDate": { "date": "2026/1/20", "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": "CA343724569/MONDO:0005338/019/ci/CA343724569/MONDO:0005338/019.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1765/1767", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/1/1766", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1765", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/el/0/1663", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/ei/1/1664", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2026/1/20", "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/CA343724569/MONDO:0005338/019/el/0/1663/1665", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA343724569/MONDO:0005338/019/ci/CA343724569/MONDO:0005338/019.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "This variant has not been identified de novo.", "contributionDate": { "date": "2026/1/20", "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": "CA343724569/MONDO:0005338/019/ci/CA343724569/MONDO:0005338/019.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1663/1665", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/1/1664", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1663", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/ei/1/1736", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2026/1/20", "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/CA343724569/MONDO:0005338/019/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA343724569/MONDO:0005338/019/ci/CA343724569/MONDO:0005338/019.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "Only 1 proband with juvenile open angle glaucoma had been reported (PMID: 9535666), not meeting the ≥ 2 probands threshold required to meet PS4_Supporting.", "contributionDate": { "date": "2026/1/20", "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": "CA343724569/MONDO:0005338/019/ci/CA343724569/MONDO:0005338/019.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1735", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/el/0/1804", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/ei/1/1805", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2026/1/20", "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/CA343724569/MONDO:0005338/019/el/0/1804/1806", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA343724569/MONDO:0005338/019/ci/CA343724569/MONDO:0005338/019.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "This criterion was not met as PM2_Supporting has been met.", "contributionDate": { "date": "2026/1/20", "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": "CA343724569/MONDO:0005338/019/ci/CA343724569/MONDO:0005338/019.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1804/1806", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/1/1805", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1804", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/el/0/1588", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/ei/1/1589", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2026/1/20", "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/CA343724569/MONDO:0005338/019/el/0/1588/1590", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA343724569/MONDO:0005338/019/ci/CA343724569/MONDO:0005338/019.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "This criterion was not met as PS3_Moderate has been met.", "contributionDate": { "date": "2026/1/20", "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": "CA343724569/MONDO:0005338/019/ci/CA343724569/MONDO:0005338/019.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1588/1590", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/1/1589", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1588", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/el/0/1654", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/ei/1/1655", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2026/1/20", "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/CA343724569/MONDO:0005338/019/el/0/1654/1656", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA343724569/MONDO:0005338/019/ci/CA343724569/MONDO:0005338/019.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "This is not an intronic, synonymous or non-coding variant.", "contributionDate": { "date": "2026/1/20", "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": "CA343724569/MONDO:0005338/019/ci/CA343724569/MONDO:0005338/019.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1654/1656", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/1/1655", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1654", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/el/0/1774", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/ei/1/1775", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2026/1/20", "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/CA343724569/MONDO:0005338/019/el/0/1774/1776", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA343724569/MONDO:0005338/019/ci/CA343724569/MONDO:0005338/019.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "Another missense variant (c.1138G>C, p.Asp380His, Grantham score = 81, ClinVar ID: 7961) in the same codon has been classified as likely pathogenic for juvenile open angle glaucoma by the ClinGen Glaucoma VCEP. The c.1139A>G, p.Asp380Gly variant has a higher Grantham score (= 94) than the previously classified amino acid change, was not predicted to affect splicing as assessed with SpliceAI (≤ 0.2), and met PP3, meeting the conditions for PM5_Supporting to apply.\nThis variant was used to apply PM5 to variant MYOC c.1139A>C, p.Asp380Ala which is located at the same amino acid residue.", "contributionDate": { "date": "2026/1/20", "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": "CA343724569/MONDO:0005338/019/ci/CA343724569/MONDO:0005338/019.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1774/1776", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/1/1775", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1774", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/el/0/1753", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/ei/1/1754", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2026/1/20", "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/CA343724569/MONDO:0005338/019/el/0/1753/1755", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA343724569/MONDO:0005338/019/ci/CA343724569/MONDO:0005338/019.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "The REVEL score = 0.964, which met the ≥ 0.932 threshold for PP3_Strong, predicting a damaging effect on MYOC function. ", "contributionDate": { "date": "2026/1/20", "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": "CA343724569/MONDO:0005338/019/ci/CA343724569/MONDO:0005338/019.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1753/1755", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/1/1754", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1753", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/el/0/1591", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/ei/1/1592", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2026/1/20", "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/CA343724569/MONDO:0005338/019/el/0/1591/1593", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA343724569/MONDO:0005338/019/ci/CA343724569/MONDO:0005338/019.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "This variant does not cause a protein length change.", "contributionDate": { "date": "2026/1/20", "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": "CA343724569/MONDO:0005338/019/ci/CA343724569/MONDO:0005338/019.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1591/1593", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/1/1592", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1591", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/el/0/1678", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/ei/1/1679", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2026/1/20", "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/CA343724569/MONDO:0005338/019/el/0/1678/1680", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA343724569/MONDO:0005338/019/ci/CA343724569/MONDO:0005338/019.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "No segregations have been reported for this variant.", "contributionDate": { "date": "2026/1/20", "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": "CA343724569/MONDO:0005338/019/ci/CA343724569/MONDO:0005338/019.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1678/1680", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/1/1679", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1678", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2026/1/20", "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/CA343724569/MONDO:0005338/019/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA343724569/MONDO:0005338/019/ci/CA343724569/MONDO:0005338/019.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "This variant was not found in any genetic ancestry group of gnomAD (v4.1.0), meeting the ≤ 0.0001 threshold set for PM2_Supporting in a genetic ancestry group of at least 10,000 alleles.", "contributionDate": { "date": "2026/1/20", "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": "CA343724569/MONDO:0005338/019/ci/CA343724569/MONDO:0005338/019.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/el/0/1825", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA343724569/MONDO:0005338/019/ei/1/1826", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "contributionDate": { "date": "2026/1/20", "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/CA343724569/MONDO:0005338/019/el/0/1825/1827", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA343724569/MONDO:0005338/019/ci/EV000001429", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50053_EP164427275875204", "id": "CG-PCER-AGENT:CG_50053_EP164427275875204", "type": "Agent" }, "comments": "The D380G protein is insoluble and has reduced secretion (J Hulleman pers. comm. unpublished data as part of the PMID:35196929 study).\nThe assay in this study meets the OddsPath threshold for PS3_Moderate (> 4.3). ", "contributionDate": { "date": "2026/1/20", "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": "CA343724569/MONDO:0005338/019/ci/EV000001429", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/35196929", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1825/1827", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/1/1826", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019/0/1825", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA343724569/MONDO:0005338/019", "metadata": { "created": "2026-01-20T23:31:17.355Z", "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": "Tue, 20 Jan 2026 23:31:17 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "2.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "b02e5129-d33a-4445-ab99-aa3dd8fc3d6d", "variant": { "@id": "https://reg.genome.network/allele/CA343724569", "id": "CAR:CA343724569", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000261.2:c.1139A>G" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000261.2:c.1139A>G" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-03T09:36:22.646Z" } }, "status": { "code": 200, "name": "OK" } }