{
  "data": {
    "@context": "https://erepo.genome.network/evrepo/api/context",
    "@id": "https://cgerepoapi/evrepo/api/summary/classification/da68b3a7-7141-49bf-9316-0019694da3a8/doc/sepio/version/1.0.0",
    "assertionMethod": {
      "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1566365955",
      "label": "ClinGen Leber Congenital Amaurosis/early onset Retinal Dystrophy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RPE65 Version 1.0.0",
      "type": "VariantPathogenicityInterpretationGuideline",
      "version": "1.0.0"
    },
    "condition": {
      "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0100368",
      "id": "MONDO:0100368",
      "label": "RPE65-related recessive retinopathy",
      "type": "GeneticCondition"
    },
    "evidenceLine": [
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA902401/MONDO:0100368/120/el/0/1717",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA902401/MONDO:0100368/120/ei/1/1718",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166",
                  "id": "CG-PCER-AGENT:CG_50082_EP170326324571166",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2024/12/12",
                  "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/CA902401/MONDO:0100368/120/el/0/1717/1719",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA902401/MONDO:0100368/120/ci/CA902401/MONDO:0100368/120.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166",
                          "id": "CG-PCER-AGENT:CG_50082_EP170326324571166",
                          "type": "Agent"
                        },
                        "comments": "This variant has been reported in at least 3 unrelated probands with early-onset severe retinal dystrophy who were homozygous for the variant (1 point, PM3, PMID: 35129589).",
                        "contributionDate": {
                          "date": "2024/12/12",
                          "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": "CA902401/MONDO:0100368/120/ci/CA902401/MONDO:0100368/120.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA902401/MONDO:0100368/120/0/1717/1719",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA902401/MONDO:0100368/120/1/1718",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA902401/MONDO:0100368/120/0/1717",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA902401/MONDO:0100368/120/el/0/1690",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA902401/MONDO:0100368/120/ei/1/1691",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166",
                  "id": "CG-PCER-AGENT:CG_50082_EP170326324571166",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2024/12/12",
                  "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/CA902401/MONDO:0100368/120/el/0/1690/1692",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA902401/MONDO:0100368/120/ci/CA902401/MONDO:0100368/120.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166",
                          "id": "CG-PCER-AGENT:CG_50082_EP170326324571166",
                          "type": "Agent"
                        },
                        "comments": "The computational predictor REVEL gives a score of 0.774, which is above the ClinGen LCA / eoRD VCEP threshold of ≥0.773 and predicts a damaging effect on RPE65 function (PP3_Moderate).",
                        "contributionDate": {
                          "date": "2024/12/12",
                          "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": "CA902401/MONDO:0100368/120/ci/CA902401/MONDO:0100368/120.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA902401/MONDO:0100368/120/0/1690/1692",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA902401/MONDO:0100368/120/1/1691",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA902401/MONDO:0100368/120/0/1690",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA902401/MONDO:0100368/120/el/0/1831",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA902401/MONDO:0100368/120/ei/1/1832",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166",
                  "id": "CG-PCER-AGENT:CG_50082_EP170326324571166",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2024/12/12",
                  "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/CA902401/MONDO:0100368/120/el/0/1831/1833",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA902401/MONDO:0100368/120/ci/CA902401/MONDO:0100368/120.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166",
                          "id": "CG-PCER-AGENT:CG_50082_EP170326324571166",
                          "type": "Agent"
                        },
                        "comments": "At least one proband harboring this variant exhibits a phenotype including clinical diagnosis of LCA (0.5 pt) and significant, documented improvement of FST or other\nmeasure of dark-adapted vision after treatment with\nLuxturna or other RPE65 gene therapy. (8.5 points, PMID: 38295874, PP4_Moderate).",
                        "contributionDate": {
                          "date": "2024/12/12",
                          "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": "CA902401/MONDO:0100368/120/ci/CA902401/MONDO:0100368/120.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA902401/MONDO:0100368/120/0/1831/1833",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA902401/MONDO:0100368/120/1/1832",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA902401/MONDO:0100368/120/0/1831",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA902401/MONDO:0100368/120/el/0/1636",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA902401/MONDO:0100368/120/ei/1/1637",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166",
                  "id": "CG-PCER-AGENT:CG_50082_EP170326324571166",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2024/12/12",
                  "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/CA902401/MONDO:0100368/120/el/0/1636/1638",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA902401/MONDO:0100368/120/ci/CA902401/MONDO:0100368/120.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50082_EP170326324571166",
                          "id": "CG-PCER-AGENT:CG_50082_EP170326324571166",
                          "type": "Agent"
                        },
                        "comments": "This variant is absent from gnomAD v4.1.0 (PM2_Supporting).",
                        "contributionDate": {
                          "date": "2024/12/12",
                          "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": "CA902401/MONDO:0100368/120/ci/CA902401/MONDO:0100368/120.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA902401/MONDO:0100368/120/0/1636/1638",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA902401/MONDO:0100368/120/1/1637",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA902401/MONDO:0100368/120/0/1636",
        "type": "EvidenceLine"
      }
    ],
    "id": "CG-PCER-VARINT:CA902401/MONDO:0100368/120",
    "metadata": {
      "created": "2024-12-20T22:36:13.582Z",
      "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, 20 Dec 2024 22:36:13 -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": "da68b3a7-7141-49bf-9316-0019694da3a8",
    "variant": {
      "@id": "https://reg.genome.network/allele/CA902401",
      "id": "CAR:CA902401",
      "relatedContextualAllele": [
        {
          "alleleName": [
            {
              "name": "NM_000329.3:c.762G>T"
            }
          ],
          "preferred": true
        }
      ],
      "type": "CAR"
    }
  },
  "metadata": {
    "rendered": {
      "by": "https://erepo.genome.network/evrepo/api/summary/srvc",
      "when": "2026-10-29T06:43:27.861Z"
    }
  },
  "status": {
    "code": 200,
    "name": "OK"
  }
}