{
  "data": {
    "@context": "https://erepo.genome.network/evrepo/api/context",
    "@id": "https://cgerepoapi/evrepo/api/summary/classification/559e3af0-c690-4060-b3d8-5105d2d1c6ac/doc/sepio/version/2.0.0",
    "assertionMethod": {
      "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/643243109",
      "label": "ClinGen RASopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for NRAS Version 2.3.0",
      "type": "VariantPathogenicityInterpretationGuideline",
      "version": "2.3.0"
    },
    "condition": {
      "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0018997",
      "id": "MONDO:0018997",
      "label": "Noonan syndrome",
      "type": "GeneticCondition"
    },
    "evidenceLine": [
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341741642/MONDO:0018997/039/el/0/1615",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341741642/MONDO:0018997/039/ei/1/1616",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081",
                  "id": "CG-PCER-AGENT:CG_50021_EP155190663717081",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2025/3/26",
                  "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"
              }
            ],
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341741642/MONDO:0018997/039/el/0/1615/1617",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA341741642/MONDO:0018997/039/ci/CA341741642/MONDO:0018997/039.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081",
                          "id": "CG-PCER-AGENT:CG_50021_EP155190663717081",
                          "type": "Agent"
                        },
                        "comments": "This variant resides within the Switch 2 region (amino acids 57 – 64), of NRAS that is defined as a critical functional domain (PM1).",
                        "contributionDate": {
                          "date": "2025/3/26",
                          "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": "CA341741642/MONDO:0018997/039/ci/CA341741642/MONDO:0018997/039.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA341741642/MONDO:0018997/039/0/1615/1617",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA341741642/MONDO:0018997/039/1/1616",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA341741642/MONDO:0018997/039/0/1615",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341741642/MONDO:0018997/039/el/0/1747",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341741642/MONDO:0018997/039/ei/1/1748",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081",
                  "id": "CG-PCER-AGENT:CG_50021_EP155190663717081",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2025/3/26",
                  "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"
              }
            ],
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341741642/MONDO:0018997/039/el/0/1747/1749",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA341741642/MONDO:0018997/039/ci/CA341741642/MONDO:0018997/039.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081",
                          "id": "CG-PCER-AGENT:CG_50021_EP155190663717081",
                          "type": "Agent"
                        },
                        "comments": "The computational predictor REVEL gives a score of 0.959, which is above the threshold of 0.7, evidence that correlates with impact to NRAS function (PP3).",
                        "contributionDate": {
                          "date": "2025/3/26",
                          "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": "CA341741642/MONDO:0018997/039/ci/CA341741642/MONDO:0018997/039.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA341741642/MONDO:0018997/039/0/1747/1749",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA341741642/MONDO:0018997/039/1/1748",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA341741642/MONDO:0018997/039/0/1747",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341741642/MONDO:0018997/039/el/0/1636",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341741642/MONDO:0018997/039/ei/1/1637",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081",
                  "id": "CG-PCER-AGENT:CG_50021_EP155190663717081",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2025/3/26",
                  "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"
              }
            ],
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341741642/MONDO:0018997/039/el/0/1636/1638",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA341741642/MONDO:0018997/039/ci/CA341741642/MONDO:0018997/039.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081",
                          "id": "CG-PCER-AGENT:CG_50021_EP155190663717081",
                          "type": "Agent"
                        },
                        "comments": "This variant is absent from gnomAD v2.1.1 (PM2_P).",
                        "contributionDate": {
                          "date": "2025/3/26",
                          "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": "CA341741642/MONDO:0018997/039/ci/CA341741642/MONDO:0018997/039.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA341741642/MONDO:0018997/039/0/1636/1638",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA341741642/MONDO:0018997/039/1/1637",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA341741642/MONDO:0018997/039/0/1636",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341741642/MONDO:0018997/039/el/0/1606",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341741642/MONDO:0018997/039/ei/1/1607",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081",
                  "id": "CG-PCER-AGENT:CG_50021_EP155190663717081",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2025/3/26",
                  "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"
              }
            ],
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341741642/MONDO:0018997/039/el/0/1606/1608",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA341741642/MONDO:0018997/039/ci/CA341741642/MONDO:0018997/039.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081",
                          "id": "CG-PCER-AGENT:CG_50021_EP155190663717081",
                          "type": "Agent"
                        },
                        "comments": "This variant has been reported in 1 proband with RASopathy (PS4_Supporting; PMID:28594414).",
                        "contributionDate": {
                          "date": "2025/3/26",
                          "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": "CA341741642/MONDO:0018997/039/ci/CA341741642/MONDO:0018997/039.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA341741642/MONDO:0018997/039/0/1606/1608",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA341741642/MONDO:0018997/039/1/1607",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA341741642/MONDO:0018997/039/0/1606",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341741642/MONDO:0018997/039/el/0/1825",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341741642/MONDO:0018997/039/ei/1/1826",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081",
                  "id": "CG-PCER-AGENT:CG_50021_EP155190663717081",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2025/3/26",
                  "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"
              }
            ],
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341741642/MONDO:0018997/039/el/0/1825/1827",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA341741642/MONDO:0018997/039/ci/CA341741642/MONDO:0018997/039.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081",
                          "id": "CG-PCER-AGENT:CG_50021_EP155190663717081",
                          "type": "Agent"
                        },
                        "comments": "ERK (and AKT) activation assays in HEK293T cells promoted enhanced activation of ERK and AKT, even in the absence of stimulation. Additionally, a higher level of NRASThr58Ile in its GTP-bound, active form was observed, indicating that this variant causes gain of function (PMID: 28594414) (PS3_Moderate).",
                        "contributionDate": {
                          "date": "2025/3/26",
                          "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": "CA341741642/MONDO:0018997/039/ci/CA341741642/MONDO:0018997/039.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA341741642/MONDO:0018997/039/0/1825/1827",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA341741642/MONDO:0018997/039/1/1826",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA341741642/MONDO:0018997/039/0/1825",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341741642/MONDO:0018997/039/el/0/1684",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341741642/MONDO:0018997/039/ei/1/1685",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081",
                  "id": "CG-PCER-AGENT:CG_50021_EP155190663717081",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2025/3/26",
                  "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"
              }
            ],
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341741642/MONDO:0018997/039/el/0/1684/1686",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA341741642/MONDO:0018997/039/ci/CA341741642/MONDO:0018997/039.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081",
                          "id": "CG-PCER-AGENT:CG_50021_EP155190663717081",
                          "type": "Agent"
                        },
                        "contributionDate": {
                          "date": "2025/3/26",
                          "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": "CA341741642/MONDO:0018997/039/ci/CA341741642/MONDO:0018997/039.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA341741642/MONDO:0018997/039/0/1684/1686",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA341741642/MONDO:0018997/039/1/1685",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Not Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA341741642/MONDO:0018997/039/0/1684",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341741642/MONDO:0018997/039/el/0/1765",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341741642/MONDO:0018997/039/ei/1/1766",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081",
                  "id": "CG-PCER-AGENT:CG_50021_EP155190663717081",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2025/3/26",
                  "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"
              }
            ],
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA341741642/MONDO:0018997/039/el/0/1765/1767",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA341741642/MONDO:0018997/039/ci/CA341741642/MONDO:0018997/039.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081",
                          "id": "CG-PCER-AGENT:CG_50021_EP155190663717081",
                          "type": "Agent"
                        },
                        "comments": "2 different missense variants, (KRAS):c.173C>T (p.Thr58Ile) (PMID: 16474405; ClinVar ID: 12588) and (HRAS):c.173C>T (p.Thr58Ile) (PMID: 18247425; ClinVar ID: 12610), in the same codon have been classified as pathogenic for RASopathy by the ClinGen RASopathy VCEP (PS1).",
                        "contributionDate": {
                          "date": "2025/3/26",
                          "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": "CA341741642/MONDO:0018997/039/ci/CA341741642/MONDO:0018997/039.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA341741642/MONDO:0018997/039/0/1765/1767",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA341741642/MONDO:0018997/039/1/1766",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA341741642/MONDO:0018997/039/0/1765",
        "type": "EvidenceLine"
      }
    ],
    "id": "CG-PCER-VARINT:CA341741642/MONDO:0018997/039",
    "metadata": {
      "created": "2025-04-01T16:33:49.093Z",
      "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, 01 Apr 2025 16:33:48 -0000",
      "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)",
      "version": "2.0.0"
    },
    "statementOutcome": {
      "@id": "https://loinc.org/LA6668-3",
      "id": "LN:LA6668-3",
      "label": "Pathogenic"
    },
    "type": "VariantPathogenicityInterpretation",
    "uuid": "559e3af0-c690-4060-b3d8-5105d2d1c6ac",
    "variant": {
      "@id": "https://reg.genome.network/allele/CA341741642",
      "id": "CAR:CA341741642",
      "relatedContextualAllele": [
        {
          "alleleName": [
            {
              "name": "NM_002524.5:c.173C>T"
            }
          ],
          "preferred": true
        }
      ],
      "relatedIdentifier": [
        {
          "label": "NM_002524.5(NRAS):c.173C>T (p.Thr58Ile)"
        }
      ],
      "type": "CAR"
    }
  },
  "metadata": {
    "rendered": {
      "by": "https://erepo.genome.network/evrepo/api/summary/srvc",
      "when": "2026-11-03T11:42:55.526Z"
    }
  },
  "status": {
    "code": 200,
    "name": "OK"
  }
}