{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/b2159f7e-5a9a-446f-8c66-b4a3a7712b54/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1570648177", "label": "ClinGen X-linked Inherited Retinal Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RS1 Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0010725", "id": "MONDO:0010725", "label": "X-linked retinoschisis", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA226843/MONDO:0010725/126/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA226843/MONDO:0010725/126/ei/1/1736", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "contributionDate": { "date": "2025/10/5", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA226843/MONDO:0010725/126/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA226843/MONDO:0010725/126/ci/CA226843/MONDO:0010725/126.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "comments": "This variant has been reported in at least 1 proband meeting the PS4 requirement of a male \ndiagnosed with X-linked retinoschisis (PMID: 9618178, PMID: 15937075). However, PS4_Supporting requires at least 2 unrelated probands, so this criterion was not met.", "contributionDate": { "date": "2025/10/5", "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": "CA226843/MONDO:0010725/126/ci/CA226843/MONDO:0010725/126.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA226843/MONDO:0010725/126/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA226843/MONDO:0010725/126/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA226843/MONDO:0010725/126/0/1735", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA226843/MONDO:0010725/126/el/0/1615", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA226843/MONDO:0010725/126/ei/1/1616", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "contributionDate": { "date": "2025/10/5", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA226843/MONDO:0010725/126/el/0/1615/1617", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA226843/MONDO:0010725/126/ci/CA226843/MONDO:0010725/126.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "comments": "This variant is a missense substitution affecting a critical amino acid residue involved in disulfide bridge formation as defined by the ClinGen X-linked IRD VCEP (PMID: 26812435). PM1_Strong is not met as this code is ineligible to be used in combination with PP3_Strong.", "contributionDate": { "date": "2025/10/5", "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": "CA226843/MONDO:0010725/126/ci/CA226843/MONDO:0010725/126.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA226843/MONDO:0010725/126/0/1615/1617", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA226843/MONDO:0010725/126/1/1616", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA226843/MONDO:0010725/126/0/1615", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA226843/MONDO:0010725/126/el/0/1696", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA226843/MONDO:0010725/126/ei/1/1697", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "contributionDate": { "date": "2025/10/5", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA226843/MONDO:0010725/126/el/0/1696/1698", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA226843/MONDO:0010725/126/ci/CA226843/MONDO:0010725/126.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "comments": "Exogenously expressed RS1 harboring the variant was subjected to gel filtration-based separation and PAGE analysis on a non‐reducing gel and exhibits defective oligomerization indicating no formation of octamers (PMID: 16361673, PS3_Supporting).", "contributionDate": { "date": "2025/10/5", "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": "CA226843/MONDO:0010725/126/ci/CA226843/MONDO:0010725/126.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA226843/MONDO:0010725/126/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA226843/MONDO:0010725/126/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA226843/MONDO:0010725/126/0/1696", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA226843/MONDO:0010725/126/el/0/1753", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA226843/MONDO:0010725/126/ei/1/1754", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "contributionDate": { "date": "2025/10/5", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA226843/MONDO:0010725/126/el/0/1753/1755", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA226843/MONDO:0010725/126/ci/CA226843/MONDO:0010725/126.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "comments": "The computational predictor REVEL gives a score of 0.984, which is above the ClinGen X-linked IRD VCEP threshold of >0.932 and predicts a damaging effect on RS1 function (PP3_Strong). The computational splicing predictor SpliceAI gives a delta score of 0.00 for all predictive splice changes, which is below the ClinGen X-linked IRD VCEP threshold of ≥0.2 and does not predict that the variant disrupts RS1 splicing.", "contributionDate": { "date": "2025/10/5", "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": "CA226843/MONDO:0010725/126/ci/CA226843/MONDO:0010725/126.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA226843/MONDO:0010725/126/0/1753/1755", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA226843/MONDO:0010725/126/1/1754", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA226843/MONDO:0010725/126/0/1753", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA226843/MONDO:0010725/126/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA226843/MONDO:0010725/126/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "contributionDate": { "date": "2025/10/5", "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" } ], "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA226843/MONDO:0010725/126/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA226843/MONDO:0010725/126/ci/CA226843/MONDO:0010725/126.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222", "id": "CG-PCER-AGENT:CG_50086_EP174775864491222", "type": "Agent" }, "comments": "This variant is absent from hemizygous individuals in gnomAD v4.1.0 (PM2_Supporting).", "contributionDate": { "date": "2025/10/5", "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": "CA226843/MONDO:0010725/126/ci/CA226843/MONDO:0010725/126.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA226843/MONDO:0010725/126/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA226843/MONDO:0010725/126/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA226843/MONDO:0010725/126/0/1636", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA226843/MONDO:0010725/126", "metadata": { "created": "2025-10-05T00:40:47.035Z", "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": "Sun, 05 Oct 2025 00:40:46 -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": "b2159f7e-5a9a-446f-8c66-b4a3a7712b54", "variant": { "@id": "https://reg.genome.network/allele/CA226843", "id": "CAR:CA226843", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000330.4:c.655T>G" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000330.4(RS1):c.655T>G (p.Cys219Gly)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-28T13:09:42.168Z" } }, "status": { "code": 200, "name": "OK" } }