{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/2156a9b5-22cf-4671-bde6-58a8a5941ae2/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1812104356", "label": "ClinGen Limb Girdle Muscular Dystrophy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for SGCA 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/CA291535993/MONDO:0015152/189/el/0/1696", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA291535993/MONDO:0015152/189/ei/1/1697", "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/CA291535993/MONDO:0015152/189/el/0/1696/1698", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA291535993/MONDO:0015152/189/ci/CA291535993/MONDO:0015152/189.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "comments": "In vitro assays have demonstrated that this variant disrupts membrane localization of the sarcoglycan complex (PMID: 22095924; PS3_Supporting). \n\n-0.44 in WashU assay, -1.9 in Lek/Yale assay", "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": "CA291535993/MONDO:0015152/189/ci/CA291535993/MONDO:0015152/189.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA291535993/MONDO:0015152/189/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA291535993/MONDO:0015152/189/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA291535993/MONDO:0015152/189/0/1696", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA291535993/MONDO:0015152/189/el/0/1678", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA291535993/MONDO:0015152/189/ei/1/1679", "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/CA291535993/MONDO:0015152/189/el/0/1678/1680", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA291535993/MONDO:0015152/189/ci/CA291535993/MONDO:0015152/189.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "comments": "The variant has been reported to segregate with autosomal recessive limb girdle muscular dystrophy in two affected siblings from one family, but phase was not confirmed (PMID: 32875335; PP1 not met).", "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": "CA291535993/MONDO:0015152/189/ci/CA291535993/MONDO:0015152/189.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA291535993/MONDO:0015152/189/0/1678/1680", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA291535993/MONDO:0015152/189/1/1679", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA291535993/MONDO:0015152/189/0/1678", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA291535993/MONDO:0015152/189/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA291535993/MONDO:0015152/189/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/CA291535993/MONDO:0015152/189/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA291535993/MONDO:0015152/189/ci/CA291535993/MONDO:0015152/189.002", "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 0.586, which is below the threshold of 0.7 (PP3 not met). ", "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": "CA291535993/MONDO:0015152/189/ci/CA291535993/MONDO:0015152/189.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA291535993/MONDO:0015152/189/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA291535993/MONDO:0015152/189/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA291535993/MONDO:0015152/189/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA291535993/MONDO:0015152/189/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA291535993/MONDO:0015152/189/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": "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/CA291535993/MONDO:0015152/189/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA291535993/MONDO:0015152/189/ci/CA291535993/MONDO:0015152/189.002", "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 heterozygous for this variant and a second diagnostic SGCA variant displayed progressive limb girdle muscle weakness and partial loss of alpha-sarcoglycan protein expression, the extent of which could not be confirmed (PP4; ClinVar SCV001432771.2 internal data communication). ", "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": "CA291535993/MONDO:0015152/189/ci/CA291535993/MONDO:0015152/189.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA291535993/MONDO:0015152/189/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA291535993/MONDO:0015152/189/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA291535993/MONDO:0015152/189/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA291535993/MONDO:0015152/189/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA291535993/MONDO:0015152/189/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/CA291535993/MONDO:0015152/189/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA291535993/MONDO:0015152/189/ci/CA291535993/MONDO:0015152/189.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "comments": "The upper bound of the 95% confidence interval of the Grpmax variant allele frequency in gnomAD v4.1.1 is 0.000004598 (10/1180008 European (non-Finnish) alleles), which is lower than the LGMD VCEP threshold (<0.00009) for PM2_Supporting, and therefore meets this criterion.", "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": "CA291535993/MONDO:0015152/189/ci/CA291535993/MONDO:0015152/189.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA291535993/MONDO:0015152/189/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA291535993/MONDO:0015152/189/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA291535993/MONDO:0015152/189/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA291535993/MONDO:0015152/189/el/0/1669", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA291535993/MONDO:0015152/189/ei/1/1670", "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/CA291535993/MONDO:0015152/189/el/0/1669/1671", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA291535993/MONDO:0015152/189/ci/CA291535993/MONDO:0015152/189.002", "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 detected in at least nine individuals with limb-girdle muscular dystrophy. Of those individuals, eight were presumed compound heterozygous for the variant and a second pathogenic or likely pathogenic variant (c.229C>T, c.739G>A, c.850C>T, c.101G>A, c.957-11C>G; 3.5 pts, PMID: 39678382, 32875335, 32528171, 12566530, 9032047, 17994539, ClinVar SCV001432771.2 internal data communication). Another individual was homozygous for the variant without reported consanguinity (0.5 pts; PMID: 18285821) (PM3_Very Strong).\n\nco-occurrence checked, classifications independent", "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": "CA291535993/MONDO:0015152/189/ci/CA291535993/MONDO:0015152/189.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA291535993/MONDO:0015152/189/0/1669/1671", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA291535993/MONDO:0015152/189/1/1670", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA291535993/MONDO:0015152/189/0/1669", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA291535993/MONDO:0015152/189", "metadata": { "created": "2026-05-07T16:25:49.891Z", "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 16:25:49 -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": "2156a9b5-22cf-4671-bde6-58a8a5941ae2", "variant": { "@id": "https://reg.genome.network/allele/CA291535993", "id": "CAR:CA291535993", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000023.4:c.92T>C" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000023.4(SGCA):c.92T>C (p.Leu31Pro)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-28T05:35:27.078Z" } }, "status": { "code": 200, "name": "OK" } }