{
  "data": {
    "@context": "https://genboree.org/evrepo/api/context",
    "@id": "https://genboree.org/evrepo/api/summary/classification/df4f3335-b54c-49a2-8016-9bbc4979399e/doc/sepio/version/1.0.0",
    "assertionMethod": {
      "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/643243137",
      "label": "ClinGen Epilepsy Sodium Channel Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for SCN1A Version 1.0.0",
      "type": "VariantPathogenicityInterpretationGuideline",
      "version": "1.0.0"
    },
    "condition": {
      "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0100135",
      "id": "MONDO:0100135",
      "label": "Dravet syndrome",
      "type": "GeneticCondition"
    },
    "evidenceLine": [
      {
        "@id": "https://genboree.org/evrepo/api/interpretation/CA303333/MONDO:0100135/067/el/0/1672",
        "evidenceItem": [
          {
            "@id": "https://genboree.org/evrepo/api/interpretation/CA303333/MONDO:0100135/067/ei/1/1673",
            "contribution": [
              {
                "agent": {
                  "@id": "https://genboree.org/evrepo/api//agent/CG_50105_EP171510967038086",
                  "id": "CG-PCER-AGENT:CG_50105_EP171510967038086",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2024/5/7",
                  "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/0010",
              "defaultStrength": {
                "@id": "https://obofoundry.org/sepio/SEPIO:0000216",
                "id": "SEPIO:0000216",
                "label": "Pathogenic Moderate"
              },
              "id": "0010",
              "label": "PM6",
              "type": "Criterion"
            },
            "evidenceLine": [
              {
                "@id": "https://genboree.org/evrepo/api/interpretation/CA303333/MONDO:0100135/067/el/0/1672/1674",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA303333/MONDO:0100135/067/ci/CA303333/MONDO:0100135/067.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://genboree.org/evrepo/api//agent/CG_50105_EP171510967038086",
                          "id": "CG-PCER-AGENT:CG_50105_EP171510967038086",
                          "type": "Agent"
                        },
                        "comments": "The authors in this paper (PMID: 20431604) sequenced all 26 coding exons of SCN1A in 63 Chinese patients with Dravet syndrome and their parents where available. The c.2303C>T variant was seen in patient # 16 in Table 1 (but the protein change noted by the authors is W768X) and it was said to be de novo without any mention of paternity/maternity confirmation. The cDNA numbering was based on GenBank sequence AB093548 and this is correct, whereas the protein residue numbering was based on P35498. In this protein sequence there is a Proline and not Tryptophan at position 768, hence it appears that the error is in the protein nomenclature. This is confirmed by looking at patient # 17 in Table 1 who had the c.2303_2306dupGACC (which starts at the same cDNA position as the variant in this spreadsheet) whose protein change is indicated as P768fsX772 i.e. there is a Proline at this position.",
                        "contributionDate": {
                          "date": "2024/5/7",
                          "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": "CA303333/MONDO:0100135/067/ci/CA303333/MONDO:0100135/067.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA303333/MONDO:0100135/067/0/1672/1674",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA303333/MONDO:0100135/067/1/1673",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA303333/MONDO:0100135/067/0/1672",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://genboree.org/evrepo/api/interpretation/CA303333/MONDO:0100135/067/el/0/1636",
        "evidenceItem": [
          {
            "@id": "https://genboree.org/evrepo/api/interpretation/CA303333/MONDO:0100135/067/ei/1/1637",
            "contribution": [
              {
                "agent": {
                  "@id": "https://genboree.org/evrepo/api//agent/CG_50105_EP171510967038086",
                  "id": "CG-PCER-AGENT:CG_50105_EP171510967038086",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2024/5/7",
                  "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://genboree.org/evrepo/api/interpretation/CA303333/MONDO:0100135/067/el/0/1636/1638",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA303333/MONDO:0100135/067/ci/CA303333/MONDO:0100135/067.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://genboree.org/evrepo/api//agent/CG_50105_EP171510967038086",
                          "id": "CG-PCER-AGENT:CG_50105_EP171510967038086",
                          "type": "Agent"
                        },
                        "contributionDate": {
                          "date": "2024/5/7",
                          "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": "CA303333/MONDO:0100135/067/ci/CA303333/MONDO:0100135/067.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA303333/MONDO:0100135/067/0/1636/1638",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA303333/MONDO:0100135/067/1/1637",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA303333/MONDO:0100135/067/0/1636",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://genboree.org/evrepo/api/interpretation/CA303333/MONDO:0100135/067/el/0/1699",
        "evidenceItem": [
          {
            "@id": "https://genboree.org/evrepo/api/interpretation/CA303333/MONDO:0100135/067/ei/1/1700",
            "contribution": [
              {
                "agent": {
                  "@id": "https://genboree.org/evrepo/api//agent/CG_50105_EP171510967038086",
                  "id": "CG-PCER-AGENT:CG_50105_EP171510967038086",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2024/5/7",
                  "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/0057",
              "defaultStrength": {
                "@id": "https://obofoundry.org/sepio/SEPIO:0000216",
                "id": "SEPIO:0000216",
                "label": "Pathogenic Moderate"
              },
              "id": "0057",
              "label": "PS4",
              "type": "Criterion"
            },
            "evidenceLine": [
              {
                "@id": "https://genboree.org/evrepo/api/interpretation/CA303333/MONDO:0100135/067/el/0/1699/1701",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA303333/MONDO:0100135/067/ci/CA303333/MONDO:0100135/067.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://genboree.org/evrepo/api//agent/CG_50105_EP171510967038086",
                          "id": "CG-PCER-AGENT:CG_50105_EP171510967038086",
                          "type": "Agent"
                        },
                        "comments": "In this paper (PMID: 35074891), they performed a retrospective multicenter cohort study comprising data from 1,018 patients with SCN1A-positive Dravet syndrome and patients with GEFS+ consecutively referred for genetic testing (March 2001-June 2020). The p.Pro768Leu variant, referred to as p.P768L, was found in the training cohort in one Italian patient diagnosed with Dravet syndrome with first seizure onset at 3 months old (patient # 241 in supplementary eTable1). No inheritance information was provided. \t\n\nThe variant was noted in two additional papers, but evidence from these papers was not scored as we could not confirm the alternate nomenclature of the variant was in fact the variant of interest (PMID: 24168886, 30921204).\n",
                        "contributionDate": {
                          "date": "2024/5/7",
                          "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": "CA303333/MONDO:0100135/067/ci/CA303333/MONDO:0100135/067.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA303333/MONDO:0100135/067/0/1699/1701",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA303333/MONDO:0100135/067/1/1700",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA303333/MONDO:0100135/067/0/1699",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://genboree.org/evrepo/api/interpretation/CA303333/MONDO:0100135/067/el/0/1690",
        "evidenceItem": [
          {
            "@id": "https://genboree.org/evrepo/api/interpretation/CA303333/MONDO:0100135/067/ei/1/1691",
            "contribution": [
              {
                "agent": {
                  "@id": "https://genboree.org/evrepo/api//agent/CG_50105_EP171510967038086",
                  "id": "CG-PCER-AGENT:CG_50105_EP171510967038086",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2024/5/7",
                  "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/0025",
              "defaultStrength": {
                "@id": "https://obofoundry.org/sepio/SEPIO:0000216",
                "id": "SEPIO:0000216",
                "label": "Pathogenic Moderate"
              },
              "id": "0025",
              "label": "PP3",
              "type": "Criterion"
            },
            "evidenceLine": [
              {
                "@id": "https://genboree.org/evrepo/api/interpretation/CA303333/MONDO:0100135/067/el/0/1690/1692",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA303333/MONDO:0100135/067/ci/CA303333/MONDO:0100135/067.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://genboree.org/evrepo/api//agent/CG_50105_EP171510967038086",
                          "id": "CG-PCER-AGENT:CG_50105_EP171510967038086",
                          "type": "Agent"
                        },
                        "contributionDate": {
                          "date": "2024/5/7",
                          "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": "CA303333/MONDO:0100135/067/ci/CA303333/MONDO:0100135/067.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA303333/MONDO:0100135/067/0/1690/1692",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA303333/MONDO:0100135/067/1/1691",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA303333/MONDO:0100135/067/0/1690",
        "type": "EvidenceLine"
      }
    ],
    "id": "CG-PCER-VARINT:CA303333/MONDO:0100135/067",
    "metadata": {
      "created": "2024-09-23T22:20:06.733Z",
      "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": "Mon, 23 Sep 2024 22:20:06 -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": "df4f3335-b54c-49a2-8016-9bbc4979399e",
    "variant": {
      "@id": "https://reg.genome.network/allele/CA303333",
      "id": "CAR:CA303333",
      "relatedContextualAllele": [
        {
          "alleleName": [
            {
              "name": "NM_001165963.4:c.2303C>T"
            }
          ],
          "preferred": true
        }
      ],
      "relatedIdentifier": [
        {
          "label": "NM_001165963.4(SCN1A):c.2303C>T (p.Pro768Leu)"
        }
      ],
      "type": "CAR"
    }
  },
  "metadata": {
    "rendered": {
      "by": "https://genboree.org/evrepo/api/summarysrvc",
      "when": "2026-05-27T22:03:57.892Z"
    }
  },
  "status": {
    "code": 200,
    "name": "OK"
  }
}