{
  "data": {
    "@context": "https://erepo.genome.network/evrepo/api/context",
    "@id": "https://cgerepoapi/evrepo/api/summary/classification/8bbf7e43-d36e-4e46-a5b9-d90f4c029bb7/doc/sepio/version/1.0.0",
    "assertionMethod": {
      "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/135637578",
      "label": "ClinGen Phenylketonuria Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for PAH Version 2.0.0",
      "type": "VariantPathogenicityInterpretationGuideline",
      "version": "2.0.0"
    },
    "condition": {
      "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0009861",
      "id": "MONDO:0009861",
      "label": "phenylketonuria",
      "type": "GeneticCondition"
    },
    "evidenceLine": [
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16020883/MONDO:0009861/006/el/0/1831",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16020883/MONDO:0009861/006/ei/1/1832",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949",
                  "id": "CG-PCER-AGENT:CG_50015_EP155190578201949",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2025/8/2",
                  "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/CA16020883/MONDO:0009861/006/el/0/1831/1833",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA16020883/MONDO:0009861/006/ci/EV000000009",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949",
                          "id": "CG-PCER-AGENT:CG_50015_EP155190578201949",
                          "type": "Agent"
                        },
                        "comments": "Patient 35: Genotype IVS4-1G>A/L293M, Classical PKU (1,200 uM or more). Urinary pterin analysis and dihydropteridine reductase (DHPR) assay were performed to exclude 6-pyruvoyl- tetrahydropterin synthase (PTPS) deficiencies.",
                        "contributionDate": {
                          "date": "2025/8/2",
                          "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": "CA16020883/MONDO:0009861/006/ci/EV000000009",
                    "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/15503242",
                    "type": "CuratorInference"
                  }
                ],
                "id": "CG-PCER-VARINT:CA16020883/MONDO:0009861/006/0/1831/1833",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA16020883/MONDO:0009861/006/1/1832",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA16020883/MONDO:0009861/006/0/1831",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16020883/MONDO:0009861/006/el/0/1696",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16020883/MONDO:0009861/006/ei/1/1697",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949",
                  "id": "CG-PCER-AGENT:CG_50015_EP155190578201949",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2025/8/2",
                  "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/CA16020883/MONDO:0009861/006/el/0/1696/1698",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA16020883/MONDO:0009861/006/ci/EV000001866",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949",
                          "id": "CG-PCER-AGENT:CG_50015_EP155190578201949",
                          "type": "Agent"
                        },
                        "comments": "A transient protein overexpression system was used. The residual activities of mutant PAH enzymes were expressed as a percentage of the wild-type PAH enzyme activity and normalized to transfection efficiencies based on β-galactosidase activities. All the PAH mutants were transfected 3 times, enzyme activities were also measured 3 times, and the mean enzyme activities were calculated. L293M has 41% mean enzyme activity (range 15–81)",
                        "contributionDate": {
                          "date": "2025/8/2",
                          "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": "CA16020883/MONDO:0009861/006/ci/EV000001866",
                    "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/16253218",
                    "type": "CuratorInference"
                  },
                  {
                    "@id": "CG-PCER:curatorInference/CA16020883/MONDO:0009861/006/ci/EV000000077",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949",
                          "id": "CG-PCER-AGENT:CG_50015_EP155190578201949",
                          "type": "Agent"
                        },
                        "comments": "96 PAH mutant alleles have been expressed to date in vitro in at least one expression system, and all were evaluated for inclusion in this study. L293M has 41% residual in vitro activity.",
                        "contributionDate": {
                          "date": "2025/8/2",
                          "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": "CA16020883/MONDO:0009861/006/ci/EV000000077",
                    "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/17924342",
                    "type": "CuratorInference"
                  }
                ],
                "id": "CG-PCER-VARINT:CA16020883/MONDO:0009861/006/0/1696/1698",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA16020883/MONDO:0009861/006/1/1697",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA16020883/MONDO:0009861/006/0/1696",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16020883/MONDO:0009861/006/el/0/1747",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16020883/MONDO:0009861/006/ei/1/1748",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949",
                  "id": "CG-PCER-AGENT:CG_50015_EP155190578201949",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2025/8/2",
                  "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/CA16020883/MONDO:0009861/006/el/0/1747/1749",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA16020883/MONDO:0009861/006/ci/CA16020883/MONDO:0009861/006.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949",
                          "id": "CG-PCER-AGENT:CG_50015_EP155190578201949",
                          "type": "Agent"
                        },
                        "comments": "Tolerated in SIFT, deleterious in PolyPhen2, MutationTaster. REVEL=0.742.",
                        "contributionDate": {
                          "date": "2025/8/2",
                          "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": "CA16020883/MONDO:0009861/006/ci/CA16020883/MONDO:0009861/006.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA16020883/MONDO:0009861/006/0/1747/1749",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA16020883/MONDO:0009861/006/1/1748",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA16020883/MONDO:0009861/006/0/1747",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16020883/MONDO:0009861/006/el/0/1636",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16020883/MONDO:0009861/006/ei/1/1637",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949",
                  "id": "CG-PCER-AGENT:CG_50015_EP155190578201949",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2025/8/2",
                  "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/CA16020883/MONDO:0009861/006/el/0/1636/1638",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA16020883/MONDO:0009861/006/ci/CA16020883/MONDO:0009861/006.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949",
                          "id": "CG-PCER-AGENT:CG_50015_EP155190578201949",
                          "type": "Agent"
                        },
                        "comments": "Absent from gnomAD v2.1.1",
                        "contributionDate": {
                          "date": "2025/8/2",
                          "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": "CA16020883/MONDO:0009861/006/ci/CA16020883/MONDO:0009861/006.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA16020883/MONDO:0009861/006/0/1636/1638",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA16020883/MONDO:0009861/006/1/1637",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA16020883/MONDO:0009861/006/0/1636",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16020883/MONDO:0009861/006/el/0/1609",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA16020883/MONDO:0009861/006/ei/1/1610",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949",
                  "id": "CG-PCER-AGENT:CG_50015_EP155190578201949",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2025/8/2",
                  "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/CA16020883/MONDO:0009861/006/el/0/1609/1611",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA16020883/MONDO:0009861/006/ci/EV000000009",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949",
                          "id": "CG-PCER-AGENT:CG_50015_EP155190578201949",
                          "type": "Agent"
                        },
                        "comments": "L293M found in trans with IVS4-1G>A (VarID 594), Pathogenic in ClinVar",
                        "contributionDate": {
                          "date": "2025/8/2",
                          "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": "CA16020883/MONDO:0009861/006/ci/EV000000009",
                    "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/15503242",
                    "type": "CuratorInference"
                  }
                ],
                "id": "CG-PCER-VARINT:CA16020883/MONDO:0009861/006/0/1609/1611",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA16020883/MONDO:0009861/006/1/1610",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA16020883/MONDO:0009861/006/0/1609",
        "type": "EvidenceLine"
      }
    ],
    "id": "CG-PCER-VARINT:CA16020883/MONDO:0009861/006",
    "metadata": {
      "created": "2025-08-02T20:05:01.482Z",
      "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": "Sat, 02 Aug 2025 20:05:01 -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": "8bbf7e43-d36e-4e46-a5b9-d90f4c029bb7",
    "variant": {
      "@id": "https://reg.genome.network/allele/CA16020883",
      "id": "CAR:CA16020883",
      "relatedContextualAllele": [
        {
          "alleleName": [
            {
              "name": "NM_000277.1:c.877T>A"
            }
          ],
          "preferred": true
        }
      ],
      "relatedIdentifier": [
        {
          "label": "NM_000277.1:c.877T>A"
        }
      ],
      "type": "CAR"
    }
  },
  "metadata": {
    "rendered": {
      "by": "https://erepo.genome.network/evrepo/api/summary/srvc",
      "when": "2026-10-29T04:41:36.129Z"
    }
  },
  "status": {
    "code": 200,
    "name": "OK"
  }
}