{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/fd3c2a91-dc99-4b9c-b672-14ea492dd40d/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1812015331", "label": "ClinGen Limb Girdle Muscular Dystrophy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for SGCG 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/CA220515/MONDO:0015152/185/el/0/1798", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA220515/MONDO:0015152/185/ei/1/1799", "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/CA220515/MONDO:0015152/185/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA220515/MONDO:0015152/185/ci/CA220515/MONDO:0015152/185.002", "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 0.000678 (30/60008 Admixed American alleles), which is higher than the LGMD VCEP threshold (<0.00009) for PM2_Supporting and therefore does not meet 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": "CA220515/MONDO:0015152/185/ci/CA220515/MONDO:0015152/185.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA220515/MONDO:0015152/185/0/1798/1800", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA220515/MONDO:0015152/185/1/1799", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA220515/MONDO:0015152/185/0/1798", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA220515/MONDO:0015152/185/el/0/1804", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA220515/MONDO:0015152/185/ei/1/1805", "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/CA220515/MONDO:0015152/185/el/0/1804/1806", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA220515/MONDO:0015152/185/ci/CA220515/MONDO:0015152/185.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "comments": "The filtering allele frequency of the variant is 0.0003599 for Admixed American alleles in gnomAD v4.1.0 (the lower threshold of the 95% CI of 30/60008), which is lower than the LGMD VCEP threshold (>0.0009) for BS1, and therefore it does not meet 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": "CA220515/MONDO:0015152/185/ci/CA220515/MONDO:0015152/185.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA220515/MONDO:0015152/185/0/1804/1806", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA220515/MONDO:0015152/185/1/1805", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA220515/MONDO:0015152/185/0/1804", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA220515/MONDO:0015152/185/el/0/1696", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA220515/MONDO:0015152/185/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/CA220515/MONDO:0015152/185/el/0/1696/1698", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA220515/MONDO:0015152/185/ci/CA220515/MONDO:0015152/185.002", "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). ", "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": "CA220515/MONDO:0015152/185/ci/CA220515/MONDO:0015152/185.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA220515/MONDO:0015152/185/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA220515/MONDO:0015152/185/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA220515/MONDO:0015152/185/0/1696", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA220515/MONDO:0015152/185/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA220515/MONDO:0015152/185/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/CA220515/MONDO:0015152/185/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA220515/MONDO:0015152/185/ci/CA220515/MONDO:0015152/185.002", "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 0.825, which is above the threshold of 0.7, evidence that correlates with impact to SGCG function (PP3).", "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": "CA220515/MONDO:0015152/185/ci/CA220515/MONDO:0015152/185.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA220515/MONDO:0015152/185/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA220515/MONDO:0015152/185/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA220515/MONDO:0015152/185/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA220515/MONDO:0015152/185/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA220515/MONDO:0015152/185/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/CA220515/MONDO:0015152/185/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA220515/MONDO:0015152/185/ci/CA220515/MONDO:0015152/185.002", "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 this variant displayed progressive limb girdle muscle weakness and reduced gamma-sarcoglycan protein expression, which is highly specific for SGCG-related LGMD (PMID: 16832103; PP4, capped with PP1_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": "CA220515/MONDO:0015152/185/ci/CA220515/MONDO:0015152/185.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA220515/MONDO:0015152/185/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA220515/MONDO:0015152/185/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA220515/MONDO:0015152/185/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA220515/MONDO:0015152/185/el/0/1651", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA220515/MONDO:0015152/185/ei/1/1652", "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/CA220515/MONDO:0015152/185/el/0/1651/1653", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA220515/MONDO:0015152/185/ci/CA220515/MONDO:0015152/185.002", "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 eight individuals with limb-girdle muscular dystrophy. Of those individuals, three were presumed compound heterozygous for the variant and a second pathogenic variant (c.525del, 1.5 pts, PMID: 32875335, 18285821). Another five individuals were homozygous for the variant (1 pt, PMID: 27708273, 16832103, 28877744, Newcastle University internal data communication) (PM3_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": "CA220515/MONDO:0015152/185/ci/CA220515/MONDO:0015152/185.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA220515/MONDO:0015152/185/0/1651/1653", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA220515/MONDO:0015152/185/1/1652", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA220515/MONDO:0015152/185/0/1651", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA220515/MONDO:0015152/185/el/0/1648", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA220515/MONDO:0015152/185/ei/1/1649", "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/CA220515/MONDO:0015152/185/el/0/1648/1650", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA220515/MONDO:0015152/185/ci/CA220515/MONDO:0015152/185.002", "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 LGMD in three affected family members from two families (PP1_Strong; PMID: 28877744, Newcastle University 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": "CA220515/MONDO:0015152/185/ci/CA220515/MONDO:0015152/185.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA220515/MONDO:0015152/185/0/1648/1650", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA220515/MONDO:0015152/185/1/1649", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA220515/MONDO:0015152/185/0/1648", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA220515/MONDO:0015152/185", "metadata": { "created": "2026-05-07T15:58:34.444Z", "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 15:58:34 -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": "fd3c2a91-dc99-4b9c-b672-14ea492dd40d", "variant": { "@id": "https://reg.genome.network/allele/CA220515", "id": "CAR:CA220515", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000231.3:c.787G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000231.3(SGCG):c.787G>A (p.Glu263Lys)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-02T18:23:05.350Z" } }, "status": { "code": 200, "name": "OK" } }