{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/6a0b022e-c6fa-41f9-be9a-932371360f78/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/CA400177765/MONDO:0015152/189/el/0/1678", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400177765/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/CA400177765/MONDO:0015152/189/el/0/1678/1680", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400177765/MONDO:0015152/189/ci/CA400177765/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 one affected family member (PP1; PMID: 12566530).", "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": "CA400177765/MONDO:0015152/189/ci/CA400177765/MONDO:0015152/189.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400177765/MONDO:0015152/189/0/1678/1680", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400177765/MONDO:0015152/189/1/1679", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400177765/MONDO:0015152/189/0/1678", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400177765/MONDO:0015152/189/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400177765/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/CA400177765/MONDO:0015152/189/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400177765/MONDO:0015152/189/ci/CA400177765/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 0.962, which is above the threshold of 0.7, evidence that correlates with impact to SGCA function (PP3). \n\nSpliceAI: 0.0400", "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": "CA400177765/MONDO:0015152/189/ci/CA400177765/MONDO:0015152/189.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400177765/MONDO:0015152/189/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400177765/MONDO:0015152/189/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400177765/MONDO:0015152/189/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400177765/MONDO:0015152/189/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400177765/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/CA400177765/MONDO:0015152/189/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400177765/MONDO:0015152/189/ci/CA400177765/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 (95% CI) of the Grpmax variant allele frequency in gnomAD v4.1.1 is 0.0000175 (13/1179600 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": "CA400177765/MONDO:0015152/189/ci/CA400177765/MONDO:0015152/189.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400177765/MONDO:0015152/189/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400177765/MONDO:0015152/189/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400177765/MONDO:0015152/189/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400177765/MONDO:0015152/189/el/0/1825", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400177765/MONDO:0015152/189/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/CA400177765/MONDO:0015152/189/el/0/1825/1827", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400177765/MONDO:0015152/189/ci/CA400177765/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 assay in an heterologous cell system has demonstrated that this variant disrupts membrane localization of the sarcoglycan complex (PS3_Moderate, Washington University internal data).\n\nVariant was tested by Gabe Haller's team using their previously reported approach for SGCB variants. The assay has been clinically validated with over 11 control variants. The variant presented a score <-0.5, which is the threshold for non-functional variants that was used for SGCB. \n\nscore -0.73 in WashU assay, -2.62 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": "CA400177765/MONDO:0015152/189/ci/CA400177765/MONDO:0015152/189.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400177765/MONDO:0015152/189/0/1825/1827", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400177765/MONDO:0015152/189/1/1826", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400177765/MONDO:0015152/189/0/1825", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400177765/MONDO:0015152/189/el/0/1738", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400177765/MONDO:0015152/189/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/CA400177765/MONDO:0015152/189/el/0/1738/1740", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400177765/MONDO:0015152/189/ci/CA400177765/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 homozygous for this variant displayed progressive limb girdle muscle weakness and absent alpha-sarcoglycan protein expression, which is highly specific for SGCA-related LGMD (PP4_Strong; PMID: 12566530).", "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": "CA400177765/MONDO:0015152/189/ci/CA400177765/MONDO:0015152/189.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400177765/MONDO:0015152/189/0/1738/1740", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400177765/MONDO:0015152/189/1/1739", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400177765/MONDO:0015152/189/0/1738", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400177765/MONDO:0015152/189/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400177765/MONDO:0015152/189/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": "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/CA400177765/MONDO:0015152/189/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400177765/MONDO:0015152/189/ci/CA400177765/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 three individuals with limb-girdle muscular dystrophy (PMID: 12566530; LOVD Individual #00133346; GRASP-LGMD Consortium internal data communication). Two patients, one from a consanguineous family, were homozygous for the variant (0.75 pts; PMID: 12566530, LOVD Individual #00133346). The third patient had the likely pathogenic variant c.614C>A p.(Pro205His) in unconfirmed phase (0.25 pts, GRASP-LGMD Consortium internal data communication) (PM3). ", "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": "CA400177765/MONDO:0015152/189/ci/CA400177765/MONDO:0015152/189.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400177765/MONDO:0015152/189/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400177765/MONDO:0015152/189/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400177765/MONDO:0015152/189/0/1717", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400177765/MONDO:0015152/189", "metadata": { "created": "2026-05-07T16:23:58.806Z", "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 16:23:58 -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": "6a0b022e-c6fa-41f9-be9a-932371360f78", "variant": { "@id": "https://reg.genome.network/allele/CA400177765", "id": "CAR:CA400177765", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000023.4:c.269A>G" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000023.4(SGCA):c.269A>G (p.Tyr90Cys)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-28T02:25:23.867Z" } }, "status": { "code": 200, "name": "OK" } }