{
  "data": {
    "@context": "https://erepo.genome.network/evrepo/api/context",
    "@id": "https://cgerepoapi/evrepo/api/summary/classification/3bab5f18-d034-477e-a0f9-4537463e90bf/doc/sepio/version/1.0.0",
    "assertionMethod": {
      "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1807907463",
      "label": "ClinGen Limb Girdle Muscular Dystrophy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for DYSF Version 2.0.0",
      "type": "VariantPathogenicityInterpretationGuideline",
      "version": "2.0.0"
    },
    "condition": {
      "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0015152",
      "id": "MONDO:0015152",
      "label": "autosomal recessive limb-girdle muscular dystrophy",
      "type": "GeneticCondition"
    },
    "evidenceLine": [
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10604806/MONDO:0015152/180/el/0/1738",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10604806/MONDO:0015152/180/ei/1/1739",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418",
                  "id": "CG-PCER-AGENT:CG_50061_EP173626590511418",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2026/2/17",
                  "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/CA10604806/MONDO:0015152/180/el/0/1738/1740",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA10604806/MONDO:0015152/180/ci/CA10604806/MONDO:0015152/180.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418",
                          "id": "CG-PCER-AGENT:CG_50061_EP173626590511418",
                          "type": "Agent"
                        },
                        "comments": "At least one individual with two presumed diagnostic variants also had absent dysferlin expression in muscle, which is highly specific for DYSF-related LGMD (Jain Foundation Dysferlin Registry, internal data communication; PP4_Strong).  ",
                        "contributionDate": {
                          "date": "2026/2/17",
                          "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": "CA10604806/MONDO:0015152/180/ci/CA10604806/MONDO:0015152/180.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA10604806/MONDO:0015152/180/0/1738/1740",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA10604806/MONDO:0015152/180/1/1739",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA10604806/MONDO:0015152/180/0/1738",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10604806/MONDO:0015152/180/el/0/1717",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10604806/MONDO:0015152/180/ei/1/1718",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418",
                  "id": "CG-PCER-AGENT:CG_50061_EP173626590511418",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2026/2/17",
                  "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/CA10604806/MONDO:0015152/180/el/0/1717/1719",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA10604806/MONDO:0015152/180/ci/CA10604806/MONDO:0015152/180.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418",
                          "id": "CG-PCER-AGENT:CG_50061_EP173626590511418",
                          "type": "Agent"
                        },
                        "comments": "This variant has been observed in at least three individuals with LGMD, including two with a second pathogenic variant in unknown phase (c.5077C>T p.(Arg1693Trp), 0.5 pts, PMID: 30564623, LOVD Individual #00220833; c.1397+2dup, 0.5 pts, Jain Foundation Dysferlin Registry, internal data communication) (PM3).",
                        "contributionDate": {
                          "date": "2026/2/17",
                          "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": "CA10604806/MONDO:0015152/180/ci/CA10604806/MONDO:0015152/180.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA10604806/MONDO:0015152/180/0/1717/1719",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA10604806/MONDO:0015152/180/1/1718",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA10604806/MONDO:0015152/180/0/1717",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10604806/MONDO:0015152/180/el/0/1747",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10604806/MONDO:0015152/180/ei/1/1748",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418",
                  "id": "CG-PCER-AGENT:CG_50061_EP173626590511418",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2026/2/17",
                  "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/CA10604806/MONDO:0015152/180/el/0/1747/1749",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA10604806/MONDO:0015152/180/ci/CA10604806/MONDO:0015152/180.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418",
                          "id": "CG-PCER-AGENT:CG_50061_EP173626590511418",
                          "type": "Agent"
                        },
                        "comments": "The computational predictor REVEL gives a score of 0.82, which is above the LGMD VCEP threshold of ≥0.70 (PP3). \n\nSplice AI: 0.01",
                        "contributionDate": {
                          "date": "2026/2/17",
                          "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": "CA10604806/MONDO:0015152/180/ci/CA10604806/MONDO:0015152/180.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA10604806/MONDO:0015152/180/0/1747/1749",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA10604806/MONDO:0015152/180/1/1748",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA10604806/MONDO:0015152/180/0/1747",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10604806/MONDO:0015152/180/el/0/1636",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10604806/MONDO:0015152/180/ei/1/1637",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418",
                  "id": "CG-PCER-AGENT:CG_50061_EP173626590511418",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2026/2/17",
                  "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/CA10604806/MONDO:0015152/180/el/0/1636/1638",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA10604806/MONDO:0015152/180/ci/CA10604806/MONDO:0015152/180.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418",
                          "id": "CG-PCER-AGENT:CG_50061_EP173626590511418",
                          "type": "Agent"
                        },
                        "comments": "The highest population frequency of this variant in gnomAD v4.1.0 is 0.00002247 in the South Asian population (2/89002 chromosomes), which is less than the ClinGen LGMD VCEP threshold (<0.0001) (PM2_Supporting).",
                        "contributionDate": {
                          "date": "2026/2/17",
                          "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": "CA10604806/MONDO:0015152/180/ci/CA10604806/MONDO:0015152/180.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA10604806/MONDO:0015152/180/0/1636/1638",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA10604806/MONDO:0015152/180/1/1637",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA10604806/MONDO:0015152/180/0/1636",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10604806/MONDO:0015152/180/el/0/1825",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10604806/MONDO:0015152/180/ei/1/1826",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418",
                  "id": "CG-PCER-AGENT:CG_50061_EP173626590511418",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2026/2/17",
                  "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/CA10604806/MONDO:0015152/180/el/0/1825/1827",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA10604806/MONDO:0015152/180/ci/CA10604806/MONDO:0015152/180.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418",
                          "id": "CG-PCER-AGENT:CG_50061_EP173626590511418",
                          "type": "Agent"
                        },
                        "comments": "Immunofluorescence and 2-A assays of dysferlin membrane localization in HEK293T cells showed the Val1840Met protein did not reach the cell membrane, indicating an impact on protein function (PMID: 35028538; PS3_Moderate). ",
                        "contributionDate": {
                          "date": "2026/2/17",
                          "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": "CA10604806/MONDO:0015152/180/ci/CA10604806/MONDO:0015152/180.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA10604806/MONDO:0015152/180/0/1825/1827",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA10604806/MONDO:0015152/180/1/1826",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA10604806/MONDO:0015152/180/0/1825",
        "type": "EvidenceLine"
      }
    ],
    "id": "CG-PCER-VARINT:CA10604806/MONDO:0015152/180",
    "metadata": {
      "created": "2026-02-17T19:51:23.400Z",
      "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, 17 Feb 2026 19:51:23 -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": "3bab5f18-d034-477e-a0f9-4537463e90bf",
    "variant": {
      "@id": "https://reg.genome.network/allele/CA10604806",
      "id": "CAR:CA10604806",
      "relatedContextualAllele": [
        {
          "alleleName": [
            {
              "name": "NM_001130987.2:c.5635G>A"
            }
          ],
          "preferred": true
        }
      ],
      "relatedIdentifier": [
        {
          "label": "NM_001130987.2(DYSF):c.5635G>A (p.Val1879Met)"
        }
      ],
      "type": "CAR"
    }
  },
  "metadata": {
    "rendered": {
      "by": "https://erepo.genome.network/evrepo/api/summary/srvc",
      "when": "2026-10-27T10:40:11.085Z"
    }
  },
  "status": {
    "code": 200,
    "name": "OK"
  }
}