{
  "data": [
    {
      "@context": "https://erepo.genome.network/evrepo/api/context",
      "@id": "https://erepo.genome.network/evrepo/api/summary/classification/cab3339e-49a5-40f2-876c-fde33f971d9b/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 1.0.0",
        "type": "VariantPathogenicityInterpretationGuideline",
        "version": "1.0.0"
      },
      "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/CA347213551/MONDO:0015152/180/el/0/1828",
          "evidenceItem": [
            {
              "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA347213551/MONDO:0015152/180/ei/1/1829",
              "contribution": [
                {
                  "agent": {
                    "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418",
                    "id": "CG-PCER-AGENT:CG_50061_EP173626590511418",
                    "type": "Agent"
                  },
                  "contributionDate": {
                    "date": "2025/7/8",
                    "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/CA347213551/MONDO:0015152/180/el/0/1828/1830",
                  "evidenceItem": [
                    {
                      "@id": "CG-PCER:curatorInference/CA347213551/MONDO:0015152/180/ci/CA347213551/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": "Not in the Tominaga et al. paper. No functional studies",
                          "contributionDate": {
                            "date": "2025/7/8",
                            "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": "CA347213551/MONDO:0015152/180/ci/CA347213551/MONDO:0015152/180.002",
                      "type": "InfFromBkgrndSciKnow"
                    }
                  ],
                  "id": "CG-PCER-VARINT:CA347213551/MONDO:0015152/180/0/1828/1830",
                  "type": "EvidenceLine"
                }
              ],
              "id": "CG-PCER-VARINT:CA347213551/MONDO:0015152/180/1/1829",
              "statementOutcome": {
                "@id": "SEPIO:0000224",
                "label": "Not Met"
              },
              "type": "CriterionAssessment"
            }
          ],
          "evidenceStrength": {
            "@id": "https://obofoundry.org/sepio"
          },
          "id": "CG-PCER-VARINT:CA347213551/MONDO:0015152/180/0/1828",
          "type": "EvidenceLine"
        },
        {
          "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA347213551/MONDO:0015152/180/el/0/1717",
          "evidenceItem": [
            {
              "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA347213551/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": "2025/7/8",
                    "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/CA347213551/MONDO:0015152/180/el/0/1717/1719",
                  "evidenceItem": [
                    {
                      "@id": "CG-PCER:curatorInference/CA347213551/MONDO:0015152/180/ci/CA347213551/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 reported in three patients with LGMD (PMID: 30564623, 39548682), including in an unknown phase with a pathogenic variant (c.2163-2A>G, 0.5 pts, PMID: 30564623, LOVD Individual #00222090) and in a homozygous state in two individuals, both with known consanguinity (0.25 pts for each patient; PMID: 39548682, LOVD Individuals #00392018, #00391975) (PM3; PP4). \n\nNo other cases in LOVD, and Eurofins Ntd Llc (ga) (Emory) is only submitter in ClinVar.\n\nPhasing was not done in the GRASP participant who prompted this curation (also reported in PMID: 30564623 and as LOVD Individual #00222090); confirming the variants were in trans would give us an additional 0.5 PM3 pts but would not be sufficient to upgrade to PM3_Strong. \n\n",
                          "contributionDate": {
                            "date": "2025/7/8",
                            "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": "CA347213551/MONDO:0015152/180/ci/CA347213551/MONDO:0015152/180.002",
                      "type": "InfFromBkgrndSciKnow"
                    }
                  ],
                  "id": "CG-PCER-VARINT:CA347213551/MONDO:0015152/180/0/1717/1719",
                  "type": "EvidenceLine"
                }
              ],
              "id": "CG-PCER-VARINT:CA347213551/MONDO:0015152/180/1/1718",
              "statementOutcome": {
                "@id": "SEPIO:0000224",
                "label": "Met"
              },
              "type": "CriterionAssessment"
            }
          ],
          "evidenceStrength": {
            "@id": "https://obofoundry.org/sepio"
          },
          "id": "CG-PCER-VARINT:CA347213551/MONDO:0015152/180/0/1717",
          "type": "EvidenceLine"
        },
        {
          "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA347213551/MONDO:0015152/180/el/0/1780",
          "evidenceItem": [
            {
              "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA347213551/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": "2025/7/8",
                    "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/CA347213551/MONDO:0015152/180/el/0/1780/1782",
                  "evidenceItem": [
                    {
                      "@id": "CG-PCER:curatorInference/CA347213551/MONDO:0015152/180/ci/CA347213551/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": "c.1160G<T p.(Arg387Leu) (Variation ID: 2441157) is VUS by Revvity and Ambry. No citations, not in LOVD.\nc.1160G>A  p.(Arg387Gln) (Variation ID: 538630) is VUS by GeneDx and Natera and LB by Labcorp/Invitae. No citations, not in LOVD.\nc.1159C>T p.(Arg387Trp) (Variation ID: 287943) is VUS by 6 submitters and LB by 1. No citations aside from Nallamilli et al. (2018), who identified it 2x as a single hit per LOVD. No other cases in LOVD.\n\nNone of the other missense variants at this position look common enough to have BS1 apply but also don't seem likely to reach LP.",
                          "contributionDate": {
                            "date": "2025/7/8",
                            "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": "CA347213551/MONDO:0015152/180/ci/CA347213551/MONDO:0015152/180.002",
                      "type": "InfFromBkgrndSciKnow"
                    }
                  ],
                  "id": "CG-PCER-VARINT:CA347213551/MONDO:0015152/180/0/1780/1782",
                  "type": "EvidenceLine"
                }
              ],
              "id": "CG-PCER-VARINT:CA347213551/MONDO:0015152/180/1/1781",
              "statementOutcome": {
                "@id": "SEPIO:0000224",
                "label": "Not Met"
              },
              "type": "CriterionAssessment"
            }
          ],
          "evidenceStrength": {
            "@id": "https://obofoundry.org/sepio"
          },
          "id": "CG-PCER-VARINT:CA347213551/MONDO:0015152/180/0/1780",
          "type": "EvidenceLine"
        },
        {
          "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA347213551/MONDO:0015152/180/el/0/1747",
          "evidenceItem": [
            {
              "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA347213551/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": "2025/7/8",
                    "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/CA347213551/MONDO:0015152/180/el/0/1747/1749",
                  "evidenceItem": [
                    {
                      "@id": "CG-PCER:curatorInference/CA347213551/MONDO:0015152/180/ci/CA347213551/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 0.86, which is above the LGMD VCEP threshold of ≥0.70, evidence that correlates with impact to DYSF function (PP3). ",
                          "contributionDate": {
                            "date": "2025/7/8",
                            "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": "CA347213551/MONDO:0015152/180/ci/CA347213551/MONDO:0015152/180.002",
                      "type": "InfFromBkgrndSciKnow"
                    }
                  ],
                  "id": "CG-PCER-VARINT:CA347213551/MONDO:0015152/180/0/1747/1749",
                  "type": "EvidenceLine"
                }
              ],
              "id": "CG-PCER-VARINT:CA347213551/MONDO:0015152/180/1/1748",
              "statementOutcome": {
                "@id": "SEPIO:0000224",
                "label": "Met"
              },
              "type": "CriterionAssessment"
            }
          ],
          "evidenceStrength": {
            "@id": "https://obofoundry.org/sepio"
          },
          "id": "CG-PCER-VARINT:CA347213551/MONDO:0015152/180/0/1747",
          "type": "EvidenceLine"
        },
        {
          "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA347213551/MONDO:0015152/180/el/0/1633",
          "evidenceItem": [
            {
              "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA347213551/MONDO:0015152/180/ei/1/1634",
              "contribution": [
                {
                  "agent": {
                    "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418",
                    "id": "CG-PCER-AGENT:CG_50061_EP173626590511418",
                    "type": "Agent"
                  },
                  "contributionDate": {
                    "date": "2025/7/8",
                    "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/CA347213551/MONDO:0015152/180/el/0/1633/1635",
                  "evidenceItem": [
                    {
                      "@id": "CG-PCER:curatorInference/CA347213551/MONDO:0015152/180/ci/CA347213551/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 patient with suspected LGMD had two presumably diagnostic variants. \n\nThe GRASP participant who prompted this curation does not seem to have had a muscle biopsy; this could be a potential avenue to pursue to upgrade the classification.",
                          "contributionDate": {
                            "date": "2025/7/8",
                            "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": "CA347213551/MONDO:0015152/180/ci/CA347213551/MONDO:0015152/180.002",
                      "type": "InfFromBkgrndSciKnow"
                    }
                  ],
                  "id": "CG-PCER-VARINT:CA347213551/MONDO:0015152/180/0/1633/1635",
                  "type": "EvidenceLine"
                }
              ],
              "id": "CG-PCER-VARINT:CA347213551/MONDO:0015152/180/1/1634",
              "statementOutcome": {
                "@id": "SEPIO:0000224",
                "label": "Met"
              },
              "type": "CriterionAssessment"
            }
          ],
          "evidenceStrength": {
            "@id": "https://obofoundry.org/sepio"
          },
          "id": "CG-PCER-VARINT:CA347213551/MONDO:0015152/180/0/1633",
          "type": "EvidenceLine"
        },
        {
          "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA347213551/MONDO:0015152/180/el/0/1636",
          "evidenceItem": [
            {
              "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA347213551/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": "2025/7/8",
                    "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/CA347213551/MONDO:0015152/180/el/0/1636/1638",
                  "evidenceItem": [
                    {
                      "@id": "CG-PCER:curatorInference/CA347213551/MONDO:0015152/180/ci/CA347213551/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 minor allele frequency for this variant is 0.00002519 (1/39700 exome chromosomes) in the East Asian population in gnomAD v4.1.0, which is less than the VCEP threshold of 0.0001 (PM2_Supporting). ",
                          "contributionDate": {
                            "date": "2025/7/8",
                            "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": "CA347213551/MONDO:0015152/180/ci/CA347213551/MONDO:0015152/180.002",
                      "type": "InfFromBkgrndSciKnow"
                    }
                  ],
                  "id": "CG-PCER-VARINT:CA347213551/MONDO:0015152/180/0/1636/1638",
                  "type": "EvidenceLine"
                }
              ],
              "id": "CG-PCER-VARINT:CA347213551/MONDO:0015152/180/1/1637",
              "statementOutcome": {
                "@id": "SEPIO:0000224",
                "label": "Met"
              },
              "type": "CriterionAssessment"
            }
          ],
          "evidenceStrength": {
            "@id": "https://obofoundry.org/sepio"
          },
          "id": "CG-PCER-VARINT:CA347213551/MONDO:0015152/180/0/1636",
          "type": "EvidenceLine"
        }
      ],
      "id": "CG-PCER-VARINT:CA347213551/MONDO:0015152/180",
      "metadata": {
        "created": "2025-07-08T18:36:36.967Z",
        "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, 08 Jul 2025 18:36:36 -0000",
        "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)",
        "version": "1.0.0"
      },
      "statementOutcome": {
        "@id": "https://loinc.org/LA26333-7",
        "id": "LN:LA26333-7",
        "label": "Uncertain Significance"
      },
      "type": "VariantPathogenicityInterpretation",
      "uuid": "cab3339e-49a5-40f2-876c-fde33f971d9b",
      "variant": {
        "@id": "https://reg.genome.network/allele/CA347213551",
        "id": "CAR:CA347213551",
        "relatedContextualAllele": [
          {
            "alleleName": [
              {
                "name": "NM_001130987.2:c.1256G>C"
              }
            ],
            "preferred": true
          }
        ],
        "relatedIdentifier": [
          {
            "label": "NM_001130987.2(DYSF):c.1256G>C (p.Arg419Pro)"
          }
        ],
        "type": "CAR"
      }
    }
  ],
  "metadata": {
    "rendered": {
      "by": "https://erepo.genome.network/evrepo/api/summary/srvc",
      "when": "2026-04-08T11:20:41.063Z"
    }
  },
  "status": {
    "code": 200,
    "name": "OK"
  }
}