{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/1cba853c-6109-4411-92e9-689f08d64d17/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/CA400181014/MONDO:0015152/189/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400181014/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/CA400181014/MONDO:0015152/189/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400181014/MONDO:0015152/189/ci/CA400181014/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 0.729, which is above the threshold of 0.7, evidence that correlates with impact to SGCA 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": "CA400181014/MONDO:0015152/189/ci/CA400181014/MONDO:0015152/189.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400181014/MONDO:0015152/189/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400181014/MONDO:0015152/189/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400181014/MONDO:0015152/189/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400181014/MONDO:0015152/189/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400181014/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/CA400181014/MONDO:0015152/189/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400181014/MONDO:0015152/189/ci/CA400181014/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 highest variant allele frequency in gnomAD v4.1.1 is 0.000079054 (1/60006 Admixed American 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": "CA400181014/MONDO:0015152/189/ci/CA400181014/MONDO:0015152/189.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400181014/MONDO:0015152/189/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400181014/MONDO:0015152/189/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400181014/MONDO:0015152/189/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400181014/MONDO:0015152/189/el/0/1669", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400181014/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/CA400181014/MONDO:0015152/189/el/0/1669/1671", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400181014/MONDO:0015152/189/ci/CA400181014/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 (PMID: 10842281, 12566530, 32875335, 31268554; LOVD Individual #00133494), including in a homozygous state in two unrelated patients, one of whom had known familial consanguinity (0.75 pts, PMID: 12566530, 31268554). In seven patients, it was reported in unconfirmed phase with a pathogenic variant (c.229C>T p.(Arg77Cys), c.739G>A p.(Val247Met), c.850C>T p.(Arg284Cys); 3.5 pts; PMID: 10842281, 12566530, 32875335, 31268554; LOVD: #00133494) (PM3_Very Strong). \n\nco-occurrence checked, variant 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": "CA400181014/MONDO:0015152/189/ci/CA400181014/MONDO:0015152/189.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400181014/MONDO:0015152/189/0/1669/1671", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400181014/MONDO:0015152/189/1/1670", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400181014/MONDO:0015152/189/0/1669", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400181014/MONDO:0015152/189/el/0/1825", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400181014/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/CA400181014/MONDO:0015152/189/el/0/1825/1827", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400181014/MONDO:0015152/189/ci/CA400181014/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": "An in vitro assay in a heterologous cell system has demonstrated that this variant disrupts membrane localization of the sarcoglycan complex, indicating disruption of protein function (PS3_Moderate, Washington University internal data).\n\n\nscore -1.28 in WashU assay, -2.47 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": "CA400181014/MONDO:0015152/189/ci/CA400181014/MONDO:0015152/189.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400181014/MONDO:0015152/189/0/1825/1827", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400181014/MONDO:0015152/189/1/1826", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400181014/MONDO:0015152/189/0/1825", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400181014/MONDO:0015152/189/el/0/1630", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400181014/MONDO:0015152/189/ei/1/1631", "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/CA400181014/MONDO:0015152/189/el/0/1630/1632", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400181014/MONDO:0015152/189/ci/CA400181014/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 reported to segregate with autosomal recessive LGMD in three affected individuals from one family (PP1_Moderate; PMID: 10842281,12566530). \n\nOne variant shown to be paternally inherited. Given there are three affected siblings, I think we can score.", "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": "CA400181014/MONDO:0015152/189/ci/CA400181014/MONDO:0015152/189.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400181014/MONDO:0015152/189/0/1630/1632", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400181014/MONDO:0015152/189/1/1631", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400181014/MONDO:0015152/189/0/1630", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400181014/MONDO:0015152/189/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA400181014/MONDO:0015152/189/ei/1/1832", "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/CA400181014/MONDO:0015152/189/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA400181014/MONDO:0015152/189/ci/CA400181014/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_Moderate, capped with PP1_Moderate; 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": "CA400181014/MONDO:0015152/189/ci/CA400181014/MONDO:0015152/189.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA400181014/MONDO:0015152/189/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400181014/MONDO:0015152/189/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA400181014/MONDO:0015152/189/0/1831", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA400181014/MONDO:0015152/189", "metadata": { "created": "2026-05-07T16:26:39.918Z", "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 16:26:39 -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": "1cba853c-6109-4411-92e9-689f08d64d17", "variant": { "@id": "https://reg.genome.network/allele/CA400181014", "id": "CAR:CA400181014", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000023.4:c.724G>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000023.4(SGCA):c.724G>T (p.Val242Phe)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-15T16:36:07.749Z" } }, "status": { "code": 200, "name": "OK" } }