{
  "data": {
    "@context": "https://erepo.genome.network/evrepo/api/context",
    "@id": "https://cgerepoapi/evrepo/api/summary/classification/8840b314-5470-4e47-a2c2-e1874b6f368d/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/CA222218/MONDO:0015152/180/el/0/1609",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA222218/MONDO:0015152/180/ei/1/1610",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418",
                  "id": "CG-PCER-AGENT:CG_50061_EP173626590511418",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2026/5/7",
                  "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"
              }
            ],
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA222218/MONDO:0015152/180/el/0/1609/1611",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA222218/MONDO:0015152/180/ci/CA222218/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 identified in one individual with progressive limb girdle muscle weakness, in whom it was reported in unconfirmed phase with a pathogenic variant (NM_003494.4: c.1663C>T p.(Arg555Trp), 0.5 pts, Jain Foundation Dysferlin Registry internal data communication; PM3_Supporting).\n\nCo-occurrence cannot be assessed because this variant is absent from gnomAD \n\nno other cases identified\nnot in LOVD\nVUS by Revvity - did not respond to request \nVUS by Eurofins - 1 single hit\n\n\n",
                        "contributionDate": {
                          "date": "2026/5/7",
                          "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": "CA222218/MONDO:0015152/180/ci/CA222218/MONDO:0015152/180.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA222218/MONDO:0015152/180/0/1609/1611",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA222218/MONDO:0015152/180/1/1610",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA222218/MONDO:0015152/180/0/1609",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA222218/MONDO:0015152/180/el/0/1747",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA222218/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": "2026/5/7",
                  "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"
              }
            ],
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA222218/MONDO:0015152/180/el/0/1747/1749",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA222218/MONDO:0015152/180/ci/CA222218/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 0.777, which is above the LGMD VCEP threshold of ≥0.70, evidence that correlates with impact to DYSF function (PP3).\n\nSpliceAI: no spice effect\n",
                        "contributionDate": {
                          "date": "2026/5/7",
                          "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": "CA222218/MONDO:0015152/180/ci/CA222218/MONDO:0015152/180.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA222218/MONDO:0015152/180/0/1747/1749",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA222218/MONDO:0015152/180/1/1748",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA222218/MONDO:0015152/180/0/1747",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA222218/MONDO:0015152/180/el/0/1636",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA222218/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": "2026/5/7",
                  "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"
              }
            ],
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA222218/MONDO:0015152/180/el/0/1636/1638",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA222218/MONDO:0015152/180/ci/CA222218/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 is absent from gnomAD v.4.1.0, meeting the criteria for PM2_Supporting.\n",
                        "contributionDate": {
                          "date": "2026/5/7",
                          "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": "CA222218/MONDO:0015152/180/ci/CA222218/MONDO:0015152/180.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA222218/MONDO:0015152/180/0/1636/1638",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA222218/MONDO:0015152/180/1/1637",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA222218/MONDO:0015152/180/0/1636",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA222218/MONDO:0015152/180/el/0/1825",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA222218/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": "2026/5/7",
                  "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"
              }
            ],
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA222218/MONDO:0015152/180/el/0/1825/1827",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA222218/MONDO:0015152/180/ci/CA222218/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 Leu266Arg protein did not reach the cell membrane, indicating an impact on protein function (PMID: 35028538) (PS3_Moderate).",
                        "contributionDate": {
                          "date": "2026/5/7",
                          "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": "CA222218/MONDO:0015152/180/ci/CA222218/MONDO:0015152/180.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA222218/MONDO:0015152/180/0/1825/1827",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA222218/MONDO:0015152/180/1/1826",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA222218/MONDO:0015152/180/0/1825",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA222218/MONDO:0015152/180/el/0/1738",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA222218/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": "2026/5/7",
                  "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"
              }
            ],
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA222218/MONDO:0015152/180/el/0/1738/1740",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA222218/MONDO:0015152/180/ci/CA222218/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 identified in at least one individual with LGMD and absent dysferlin in muscle and blood monocytes, in whom it was reported in unknown phase with a pathogenic variant. (Jain Foundation Dysferlin Registry internal data communication; PP4_Strong).",
                        "contributionDate": {
                          "date": "2026/5/7",
                          "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": "CA222218/MONDO:0015152/180/ci/CA222218/MONDO:0015152/180.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA222218/MONDO:0015152/180/0/1738/1740",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA222218/MONDO:0015152/180/1/1739",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA222218/MONDO:0015152/180/0/1738",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA222218/MONDO:0015152/180/el/0/1780",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA222218/MONDO:0015152/180/ei/1/1781",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418",
                  "id": "CG-PCER-AGENT:CG_50061_EP173626590511418",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2026/5/7",
                  "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"
              }
            ],
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA222218/MONDO:0015152/180/el/0/1780/1782",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA222218/MONDO:0015152/180/ci/CA222218/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": "Another missense change at the same residue, NM_003494.4: c.797T>C p.(Leu266Pro), has been reported in association with dysferlinopathy (LOVD Individual #00215299, PMID: 18853459), but the clinical significance of this variant remains uncertain (PM5_Supporting not met). \n\nDYSF c.797T>C (p.Leu266Pro) looks to be VUS : \nonly detected in one case: \nwith \"pseudo-metabolic myopathy\" and severely reduced dysferlin, in undetermined phase with c.4876delG (p.Val1626Tyrfsx8) (LOVD Individual #00215299, PMID: 18853459,17698709).\nPP4 not applied for pseudo-metabolic phenotype and 0.5 PM3 pts if frameshift curated insufficient to reach LP\nPM2_Supporting, PP3, PM5_Supporting (for c.797T>G \tp.(Leu266Arg))\n",
                        "contributionDate": {
                          "date": "2026/5/7",
                          "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": "CA222218/MONDO:0015152/180/ci/CA222218/MONDO:0015152/180.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA222218/MONDO:0015152/180/0/1780/1782",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA222218/MONDO:0015152/180/1/1781",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Not Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA222218/MONDO:0015152/180/0/1780",
        "type": "EvidenceLine"
      }
    ],
    "id": "CG-PCER-VARINT:CA222218/MONDO:0015152/180",
    "metadata": {
      "created": "2026-05-07T16:20:18.251Z",
      "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, 07 May 2026 16:20:18 -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": "8840b314-5470-4e47-a2c2-e1874b6f368d",
    "variant": {
      "@id": "https://reg.genome.network/allele/CA222218",
      "id": "CAR:CA222218",
      "relatedContextualAllele": [
        {
          "alleleName": [
            {
              "name": "NM_001130987.2:c.893T>G"
            }
          ],
          "preferred": true
        }
      ],
      "relatedIdentifier": [
        {
          "label": "NM_001130987.2(DYSF):c.893T>G (p.Leu298Arg)"
        }
      ],
      "type": "CAR"
    }
  },
  "metadata": {
    "rendered": {
      "by": "https://erepo.genome.network/evrepo/api/summary/srvc",
      "when": "2026-11-02T18:04:36.417Z"
    }
  },
  "status": {
    "code": 200,
    "name": "OK"
  }
}