{
  "data": {
    "@context": "https://erepo.genome.network/evrepo/api/context",
    "@id": "https://cgerepoapi/evrepo/api/summary/classification/415050f9-91f0-46ff-9526-a6ef4515f5b1/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": [
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        "evidenceItem": [
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            "contribution": [
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                "contributionRole": {
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            ],
            "evidenceLine": [
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                        "comments": "This variant has been identified in one individual with progressive muscle weakness, elevated serum creatine kinase, and suspected Miyoshi myopathy as well as absent dysferlin expression by blood monocyte assay, where it was identified in unconfirmed phase with a second presumed diagnostic DYSF variant (ClinVar SCV002975439.1, Jain Foundation Dysferlin Registry internal data communication; PP4_Strong).\n\n\n\n",
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                ],
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            ],
            "id": "CG-PCER-VARINT:CA1707485/MONDO:0015152/180/1/1739",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
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        "id": "CG-PCER-VARINT:CA1707485/MONDO:0015152/180/0/1738",
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                  "label": "curator role",
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            ],
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                          "id": "CG-PCER-AGENT:CG_50061_EP173626590511418",
                          "type": "Agent"
                        },
                        "comments": "This variant has been identified in at least three individuals with features consistent with LGMD (PMID: 34559919, 30564623; ClinVar SCV002975439.1, Jain Foundation Dysferlin Registry internal data communication; LOVD Individuals #00219617 and #00376017), including in unknown phase with a variant independently classified as likely pathogenic in one patient (NM_003494.4: c.1278dup p.(Lys427GlufsTer47), 0.25 pts, ClinVar SCV002975439.1, Jain Foundation Dysferlin Registry internal data communication). In another case, a second DYSF variant was not identified (PMID: 34559919, LOVD Individual #00376017). In the third individual, c.5629T>C p.(Tyr1877His) was identified in unknown phase with a pathogenic DYSF variant (NM_003494.4: c.1168G>A p.(Asp390Asn)), but this individual was also homozygous for a pathogenic variant in ANO5 (c.191dup p.(Asn64LysfsTer15), with limited phenotype detail provided (PMID: 30564623, LOVD Individual #00219617). \n\nCo-occurrence: \nc.1278dup p.(Lys427Glufs*47): not found in gnomAD v4.1.0 \nc.1168G>A p.(Asp390Asn): predicted on different haplotype in European (non-Finnish) \n\nNotes:\nNeuroMeGen, Hospital Clinico Santiago de Compostela: likely pathogenic, No contact information.\nLabcorp Genetics (formerly Invitae): VUS - included, 0.25 pts\nEurofins Ntd Llc (ga): VUS - Nallamilli case that could not be scored\n\nno other cases in LOVD, literature\n\n\n\n\n",
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                    ],
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                  }
                ],
                "id": "CG-PCER-VARINT:CA1707485/MONDO:0015152/180/0/1717/1719",
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            ],
            "id": "CG-PCER-VARINT:CA1707485/MONDO:0015152/180/1/1718",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Not Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA1707485/MONDO:0015152/180/0/1717",
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              {
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                  "label": "curator role",
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                "type": "Contribution"
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            ],
            "evidenceLine": [
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                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA1707485/MONDO:0015152/180/el/0/1780/1782",
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                        "comments": "No variants qualified.",
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                    ],
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                ],
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        ],
        "evidenceStrength": {
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        "id": "CG-PCER-VARINT:CA1707485/MONDO:0015152/180/0/1780",
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        "evidenceItem": [
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                "type": "Contribution"
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            ],
            "evidenceLine": [
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                "evidenceItem": [
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                        },
                        "comments": "The computational predictor REVEL gives a score of 0.891, which is above the LGMD VCEP threshold of ≥0.70, evidence that correlates with impact to DYSF function (PP3).\n\nSpliceAI: no splice effect.\n",
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                    ],
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                "id": "CG-PCER-VARINT:CA1707485/MONDO:0015152/180/0/1747/1749",
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            ],
            "id": "CG-PCER-VARINT:CA1707485/MONDO:0015152/180/1/1748",
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              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA1707485/MONDO:0015152/180/0/1747",
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                  "id": "SEPIO:0000516",
                  "label": "curator role",
                  "type": "ContributoryRole"
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                "type": "Contribution"
              }
            ],
            "evidenceLine": [
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                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA1707485/MONDO:0015152/180/el/0/1636/1638",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA1707485/MONDO:0015152/180/ci/CA1707485/MONDO:0015152/180.002",
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                          "type": "Agent"
                        },
                        "comments": "The upper bound of the 95% confidence interval of the Grpmax variant allele frequency in gnomAD v4.1.0 is 0.00000657 (3/1180038 European (non-Finnish) chromosomes), which is less than the ClinGen LGMD VCEP threshold (<0.0001) (PM2_Supporting). \n\n",
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                "id": "CG-PCER-VARINT:CA1707485/MONDO:0015152/180/0/1636/1638",
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            "id": "CG-PCER-VARINT:CA1707485/MONDO:0015152/180/1/1637",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
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          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
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        "id": "CG-PCER-VARINT:CA1707485/MONDO:0015152/180/0/1636",
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                  "@id": "https://obofoundry.org/sepio/0000156",
                  "id": "SEPIO:0000516",
                  "label": "curator role",
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            ],
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                    ],
                    "id": "CA1707485/MONDO:0015152/180/ci/CA1707485/MONDO:0015152/180.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA1707485/MONDO:0015152/180/0/1828/1830",
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            ],
            "id": "CG-PCER-VARINT:CA1707485/MONDO:0015152/180/1/1829",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Not Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA1707485/MONDO:0015152/180/0/1828",
        "type": "EvidenceLine"
      }
    ],
    "id": "CG-PCER-VARINT:CA1707485/MONDO:0015152/180",
    "metadata": {
      "created": "2026-05-07T16:22:11.848Z",
      "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 16:22:11 -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": "415050f9-91f0-46ff-9526-a6ef4515f5b1",
    "variant": {
      "@id": "https://reg.genome.network/allele/CA1707485",
      "id": "CAR:CA1707485",
      "relatedContextualAllele": [
        {
          "alleleName": [
            {
              "name": "NM_001130987.2:c.5746T>C"
            }
          ],
          "preferred": true
        }
      ],
      "relatedIdentifier": [
        {
          "label": "NM_001130987.2(DYSF):c.5746T>C (p.Tyr1916His)"
        }
      ],
      "type": "CAR"
    }
  },
  "metadata": {
    "rendered": {
      "by": "https://erepo.genome.network/evrepo/api/summary/srvc",
      "when": "2026-11-03T17:54:50.901Z"
    }
  },
  "status": {
    "code": 200,
    "name": "OK"
  }
}