{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/479a249a-0ed0-40c2-addc-c723d5e77120/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1812056141", "label": "ClinGen Limb Girdle Muscular Dystrophy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for CAPN3 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/CA347357/MONDO:0015152/187/el/0/1594", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA347357/MONDO:0015152/187/ei/1/1595", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "contributionDate": { "date": "2026/4/9", "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/CA347357/MONDO:0015152/187/el/0/1594/1596", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA347357/MONDO:0015152/187/ci/CA347357/MONDO:0015152/187.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "comments": "The NM_000070.3: c.327_328dup p.(Arg110ProfsTer18) variant is a frameshift variant predicted to cause a premature stop codon in biologically relevant exon 2/24, leading to nonsense-mediated decay in a gene in which loss of function is an established disease mechanism (PVS1). \n\nChecked SpliceAI (0.010) - no predicted impact", "contributionDate": { "date": "2026/4/9", "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": "CA347357/MONDO:0015152/187/ci/CA347357/MONDO:0015152/187.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA347357/MONDO:0015152/187/0/1594/1596", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA347357/MONDO:0015152/187/1/1595", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA347357/MONDO:0015152/187/0/1594", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA347357/MONDO:0015152/187/el/0/1738", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA347357/MONDO:0015152/187/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": "2026/4/9", "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/CA347357/MONDO:0015152/187/el/0/1738/1740", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA347357/MONDO:0015152/187/ci/CA347357/MONDO:0015152/187.002", "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 individual with this variant and a second presumed diagnostic CAPN3 variant displayed progressive limb girdle muscle weakness as well as absent CAPN3 expression in skeletal muscle, which is highly specific for CAPN3-related LGMD (PMID: 18055493, LOVD Individual #00214565; PP4_Strong).", "contributionDate": { "date": "2026/4/9", "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": "CA347357/MONDO:0015152/187/ci/CA347357/MONDO:0015152/187.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA347357/MONDO:0015152/187/0/1738/1740", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA347357/MONDO:0015152/187/1/1739", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA347357/MONDO:0015152/187/0/1738", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA347357/MONDO:0015152/187/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA347357/MONDO:0015152/187/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": "2026/4/9", "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/CA347357/MONDO:0015152/187/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA347357/MONDO:0015152/187/ci/CA347357/MONDO:0015152/187.002", "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 v4.1.0 is 0.000076118 (74/1179616 European (non-Finnish) alleles), which is less than the VCEP threshold of 0.0001 (PM2_Supporting). ", "contributionDate": { "date": "2026/4/9", "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": "CA347357/MONDO:0015152/187/ci/CA347357/MONDO:0015152/187.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA347357/MONDO:0015152/187/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA347357/MONDO:0015152/187/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA347357/MONDO:0015152/187/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA347357/MONDO:0015152/187/el/0/1609", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA347357/MONDO:0015152/187/ei/1/1610", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50061_EP173626590511418", "id": "CG-PCER-AGENT:CG_50061_EP173626590511418", "type": "Agent" }, "contributionDate": { "date": "2026/4/9", "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/CA347357/MONDO:0015152/187/el/0/1609/1611", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA347357/MONDO:0015152/187/ci/CA347357/MONDO:0015152/187.002", "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 identified in at least two patients with features consistent with LGMD (PMID: 30564623, 1805549; LOVD CAPN3_000440), including in unconfirmed phase with a pathogenic variant (c.1993-1G>A, 0.5 pts, PMID: 30564623, LOVD Individual #00220608) (PM3_Supporting). \n\nc.1993-1G>A is independently classified as P; co-occurrence could not be checked since one of the variants is absent from gnomAD v2 exomes", "contributionDate": { "date": "2026/4/9", "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": "CA347357/MONDO:0015152/187/ci/CA347357/MONDO:0015152/187.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA347357/MONDO:0015152/187/0/1609/1611", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA347357/MONDO:0015152/187/1/1610", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA347357/MONDO:0015152/187/0/1609", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA347357/MONDO:0015152/187", "metadata": { "created": "2026-04-09T23:53:31.689Z", "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, 09 Apr 2026 23:53:31 -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": "479a249a-0ed0-40c2-addc-c723d5e77120", "variant": { "@id": "https://reg.genome.network/allele/CA347357", "id": "CAR:CA347357", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000070.3:c.327_328dup" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000070.3(CAPN3):c.327_328dup (p.Arg110fs)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-14T02:35:40.398Z" } }, "status": { "code": 200, "name": "OK" } }