{
  "data": {
    "@context": "https://erepo.genome.network/evrepo/api/context",
    "@id": "https://cgerepoapi/evrepo/api/summary/classification/04282c13-07a5-4da1-99d4-2f0d6b186202/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/CA412378923/MONDO:0010725/126/el/0/1747",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412378923/MONDO:0010725/126/ei/1/1748",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222",
                  "id": "CG-PCER-AGENT:CG_50086_EP174775864491222",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2026/9/26",
                  "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"
              }
            ],
            "criterion": {
              "@id": "https://obofoundry.org/sepio/clingen/0062",
              "defaultStrength": {
                "@id": "https://obofoundry.org/sepio/SEPIO:0000329",
                "id": "SEPIO:0000329",
                "label": "Pathogenic Supporting"
              },
              "id": "0062",
              "label": "PP3",
              "type": "Criterion"
            },
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412378923/MONDO:0010725/126/el/0/1747/1749",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA412378923/MONDO:0010725/126/ci/CA412378923/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 0.318, which is between the ClinGen X-linked IRD VCEP threshold of 0.290 and 0.664 and does not predict a damaging effect on RS1 function. The splicing impact predictor SpliceAI gives a score of 0.31, which is above the ClinGen X-linked IRD VCEP recommended threshold of ≥0.2 and predicts an impact on splicing. This code was combined with PS3_Supporting.",
                        "contributionDate": {
                          "date": "2026/9/26",
                          "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": "CA412378923/MONDO:0010725/126/ci/CA412378923/MONDO:0010725/126.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA412378923/MONDO:0010725/126/0/1747/1749",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA412378923/MONDO:0010725/126/1/1748",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Not Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA412378923/MONDO:0010725/126/0/1747",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412378923/MONDO:0010725/126/el/0/1633",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412378923/MONDO:0010725/126/ei/1/1634",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222",
                  "id": "CG-PCER-AGENT:CG_50086_EP174775864491222",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2026/9/26",
                  "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"
              }
            ],
            "criterion": {
              "@id": "https://obofoundry.org/sepio/clingen/0063",
              "defaultStrength": {
                "@id": "https://obofoundry.org/sepio/SEPIO:0000329",
                "id": "SEPIO:0000329",
                "label": "Pathogenic Supporting"
              },
              "id": "0063",
              "label": "PP4",
              "type": "Criterion"
            },
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412378923/MONDO:0010725/126/el/0/1633/1635",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA412378923/MONDO:0010725/126/ci/CA412378923/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": "At least one proband harboring this variant exhibits the following phenotypes, including the appearance of schisis and reduced visual acuity before age 13 years, which together are specific for X-linked retinoschisis (PMID: 20809529, PP4).",
                        "contributionDate": {
                          "date": "2026/9/26",
                          "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": "CA412378923/MONDO:0010725/126/ci/CA412378923/MONDO:0010725/126.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA412378923/MONDO:0010725/126/0/1633/1635",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA412378923/MONDO:0010725/126/1/1634",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA412378923/MONDO:0010725/126/0/1633",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412378923/MONDO:0010725/126/el/0/1636",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412378923/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": "2026/9/26",
                  "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"
              }
            ],
            "criterion": {
              "@id": "https://obofoundry.org/sepio/clingen/0030",
              "defaultStrength": {
                "@id": "https://obofoundry.org/sepio/SEPIO:0000329",
                "id": "SEPIO:0000329",
                "label": "Pathogenic Supporting"
              },
              "id": "0030",
              "label": "PM2",
              "type": "Criterion"
            },
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412378923/MONDO:0010725/126/el/0/1636/1638",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA412378923/MONDO:0010725/126/ci/CA412378923/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": "2026/9/26",
                          "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": "CA412378923/MONDO:0010725/126/ci/CA412378923/MONDO:0010725/126.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA412378923/MONDO:0010725/126/0/1636/1638",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA412378923/MONDO:0010725/126/1/1637",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA412378923/MONDO:0010725/126/0/1636",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412378923/MONDO:0010725/126/el/0/1828",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412378923/MONDO:0010725/126/ei/1/1829",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222",
                  "id": "CG-PCER-AGENT:CG_50086_EP174775864491222",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2026/9/26",
                  "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"
              }
            ],
            "criterion": {
              "@id": "https://obofoundry.org/sepio/clingen/0052",
              "defaultStrength": {
                "@id": "https://obofoundry.org/sepio/SEPIO:0000330",
                "id": "SEPIO:0000330",
                "label": "Pathogenic Strong"
              },
              "id": "0052",
              "label": "PS3",
              "type": "Criterion"
            },
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412378923/MONDO:0010725/126/el/0/1828/1830",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA412378923/MONDO:0010725/126/ci/https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpubmed%2F20809529",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222",
                          "id": "CG-PCER-AGENT:CG_50086_EP174775864491222",
                          "type": "Agent"
                        },
                        "comments": "Vijayasarathy et al. Western blotting with little to no signal, as well as Sanger sequencing of cDNA clones showing skipping of either exon 2 or both exons 1 and 2.",
                        "contributionDate": {
                          "date": "2026/9/26",
                          "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": "CA412378923/MONDO:0010725/126/ci/https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpubmed%2F20809529",
                    "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/20809529",
                    "type": "CuratorInference"
                  }
                ],
                "id": "CG-PCER-VARINT:CA412378923/MONDO:0010725/126/0/1828/1830",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA412378923/MONDO:0010725/126/1/1829",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Not Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA412378923/MONDO:0010725/126/0/1828",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412378923/MONDO:0010725/126/el/0/1630",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412378923/MONDO:0010725/126/ei/1/1631",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222",
                  "id": "CG-PCER-AGENT:CG_50086_EP174775864491222",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2026/9/26",
                  "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"
              }
            ],
            "criterion": {
              "@id": "https://obofoundry.org/sepio/clingen/0040",
              "defaultStrength": {
                "@id": "https://obofoundry.org/sepio/SEPIO:0000216",
                "id": "SEPIO:0000216",
                "label": "Pathogenic Moderate"
              },
              "id": "0040",
              "label": "PP1",
              "type": "Criterion"
            },
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412378923/MONDO:0010725/126/el/0/1630/1632",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA412378923/MONDO:0010725/126/ci/CA412378923/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 variant has been reported to segregate through at least 2 meioses in one family (PP1_moderate; PMID: 20809529).",
                        "contributionDate": {
                          "date": "2026/9/26",
                          "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": "CA412378923/MONDO:0010725/126/ci/CA412378923/MONDO:0010725/126.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA412378923/MONDO:0010725/126/0/1630/1632",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA412378923/MONDO:0010725/126/1/1631",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA412378923/MONDO:0010725/126/0/1630",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412378923/MONDO:0010725/126/el/0/1594",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412378923/MONDO:0010725/126/ei/1/1595",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50086_EP174775864491222",
                  "id": "CG-PCER-AGENT:CG_50086_EP174775864491222",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2026/9/26",
                  "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"
              }
            ],
            "criterion": {
              "@id": "https://obofoundry.org/sepio/clingen/0017",
              "defaultStrength": {
                "@id": "https://obofoundry.org/sepio/SEPIO:0000220",
                "id": "SEPIO:0000220",
                "label": "Pathogenic Very Strong"
              },
              "id": "0017",
              "label": "PVS1",
              "type": "Criterion"
            },
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA412378923/MONDO:0010725/126/el/0/1594/1596",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA412378923/MONDO:0010725/126/ci/CA412378923/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 splicing impact predictor SpliceAI gives the variant a score of 0.31, which is above the ClinGen X-linked IRD VCEP recommended threshold of ≥0.2 and predicts a damaging impact on splicing. Functional studies confirm that the variant triggers either exon 2 or both exons 1 and 2 skipping in all transcripts (PMID: 20809529). While these in silico and experimental findings would normally be counted under the PP3 and PS3_Supporting codes, respectively, in combination, they have been counted as evidence of a loss-of-function effect (PVS1_RNA). ",
                        "contributionDate": {
                          "date": "2026/9/26",
                          "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": "CA412378923/MONDO:0010725/126/ci/CA412378923/MONDO:0010725/126.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA412378923/MONDO:0010725/126/0/1594/1596",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA412378923/MONDO:0010725/126/1/1595",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA412378923/MONDO:0010725/126/0/1594",
        "type": "EvidenceLine"
      }
    ],
    "id": "CG-PCER-VARINT:CA412378923/MONDO:0010725/126",
    "metadata": {
      "created": "2026-10-15T19:04:03.745Z",
      "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, 15 Oct 2026 19:04:03 -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": "04282c13-07a5-4da1-99d4-2f0d6b186202",
    "variant": {
      "@id": "https://reg.genome.network/allele/CA412378923",
      "id": "CAR:CA412378923",
      "relatedContextualAllele": [
        {
          "alleleName": [
            {
              "name": "NM_000330.4:c.52G>A"
            }
          ],
          "preferred": true
        }
      ],
      "relatedIdentifier": [
        {
          "label": "NM_000330.4:c.52G>A"
        }
      ],
      "type": "CAR"
    }
  },
  "metadata": {
    "rendered": {
      "by": "https://erepo.genome.network/evrepo/api/summary/srvc",
      "when": "2026-11-02T07:18:06.463Z"
    }
  },
  "status": {
    "code": 200,
    "name": "OK"
  }
}