{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/0e7e4644-f85d-408c-9ff6-97a3442c196e/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1616197506", "label": "ClinGen Congenital Myopathies Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MTM1 Version 1.0.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0018947", "id": "MONDO:0018947", "label": "centronuclear myopathy", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415256307/MONDO:0018947/149/el/0/1699", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415256307/MONDO:0018947/149/ei/1/1700", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50031_EP172779037880653", "id": "CG-PCER-AGENT:CG_50031_EP172779037880653", "type": "Agent" }, "contributionDate": { "date": "2025/12/9", "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/CA415256307/MONDO:0018947/149/el/0/1699/1701", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA415256307/MONDO:0018947/149/ci/CA415256307/MONDO:0018947/149.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50031_EP172779037880653", "id": "CG-PCER-AGENT:CG_50031_EP172779037880653", "type": "Agent" }, "comments": "This variant has been reported in 3 probands with features of centronuclear myopathy (PS4_moderate; PMIDs: 10063835, 12522554; Beggs Laboratory, Boston Children’s Hospital). ", "contributionDate": { "date": "2025/12/9", "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": "CA415256307/MONDO:0018947/149/ci/CA415256307/MONDO:0018947/149.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA415256307/MONDO:0018947/149/0/1699/1701", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA415256307/MONDO:0018947/149/1/1700", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA415256307/MONDO:0018947/149/0/1699", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415256307/MONDO:0018947/149/el/0/1696", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415256307/MONDO:0018947/149/ei/1/1697", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50031_EP172779037880653", "id": "CG-PCER-AGENT:CG_50031_EP172779037880653", "type": "Agent" }, "contributionDate": { "date": "2025/12/9", "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/CA415256307/MONDO:0018947/149/el/0/1696/1698", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA415256307/MONDO:0018947/149/ci/EV000001934", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50031_EP172779037880653", "id": "CG-PCER-AGENT:CG_50031_EP172779037880653", "type": "Agent" }, "comments": "Expression analysis was done via western blot for total protein-containing lysate from HEK293T cells transfected by corresponding plasmids. The loading control was GADPH, and the probing of the band for GADPH was done at 37 kDA. The wild-type and mutants were seen below 75 kDA, the anticipated length. The mutant p.Trp230Cys shows low expression of MTM1 compared to the wild-type.", "contributionDate": { "date": "2025/12/9", "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": "CA415256307/MONDO:0018947/149/ci/EV000001934", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/37101954", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA415256307/MONDO:0018947/149/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA415256307/MONDO:0018947/149/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA415256307/MONDO:0018947/149/0/1696", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415256307/MONDO:0018947/149/el/0/1774", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415256307/MONDO:0018947/149/ei/1/1775", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50031_EP172779037880653", "id": "CG-PCER-AGENT:CG_50031_EP172779037880653", "type": "Agent" }, "contributionDate": { "date": "2025/12/9", "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/CA415256307/MONDO:0018947/149/el/0/1774/1776", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA415256307/MONDO:0018947/149/ci/CA415256307/MONDO:0018947/149.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50031_EP172779037880653", "id": "CG-PCER-AGENT:CG_50031_EP172779037880653", "type": "Agent" }, "comments": "Another missense variant (c.688T>C, p.Trp230Arg) [VCV000092677] in the same codon has been classified as likely pathogenic for X-linked centronuclear myopathy by the ClinGen Congenital Myopathies VCEP indicating that this residue may be critical to MTM1 function (PM5_Supporting).", "contributionDate": { "date": "2025/12/9", "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": "CA415256307/MONDO:0018947/149/ci/CA415256307/MONDO:0018947/149.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA415256307/MONDO:0018947/149/0/1774/1776", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA415256307/MONDO:0018947/149/1/1775", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA415256307/MONDO:0018947/149/0/1774", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415256307/MONDO:0018947/149/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415256307/MONDO:0018947/149/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50031_EP172779037880653", "id": "CG-PCER-AGENT:CG_50031_EP172779037880653", "type": "Agent" }, "contributionDate": { "date": "2025/12/9", "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/CA415256307/MONDO:0018947/149/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA415256307/MONDO:0018947/149/ci/CA415256307/MONDO:0018947/149.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50031_EP172779037880653", "id": "CG-PCER-AGENT:CG_50031_EP172779037880653", "type": "Agent" }, "comments": "The computational predictor REVEL gives a score of 0.901, which is above the Congenital Myopathies VCEP threshold of 0.7, evidence that correlates with impact to MTM1 function (PP3). Computational predictors consistently suggest a harmful impact (ie. damaging by SIFT, probably damaging by PolyPhen, deleterious by LRT, disease causing by MutationTaster). The variant is not predicted to impact splicing (highest SpliceAI score is 0.09 for acceptor gain). ", "contributionDate": { "date": "2025/12/9", "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": "CA415256307/MONDO:0018947/149/ci/CA415256307/MONDO:0018947/149.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA415256307/MONDO:0018947/149/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA415256307/MONDO:0018947/149/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA415256307/MONDO:0018947/149/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415256307/MONDO:0018947/149/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415256307/MONDO:0018947/149/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50031_EP172779037880653", "id": "CG-PCER-AGENT:CG_50031_EP172779037880653", "type": "Agent" }, "contributionDate": { "date": "2025/12/9", "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/CA415256307/MONDO:0018947/149/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA415256307/MONDO:0018947/149/ci/CA415256307/MONDO:0018947/149.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50031_EP172779037880653", "id": "CG-PCER-AGENT:CG_50031_EP172779037880653", "type": "Agent" }, "comments": "This variant is absent from gnomAD v4.1.0 (PM2_supporting). Coverage of the gene is this region is adequate.", "contributionDate": { "date": "2025/12/9", "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": "CA415256307/MONDO:0018947/149/ci/CA415256307/MONDO:0018947/149.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA415256307/MONDO:0018947/149/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA415256307/MONDO:0018947/149/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA415256307/MONDO:0018947/149/0/1636", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA415256307/MONDO:0018947/149", "metadata": { "created": "2025-12-09T18:13:12.325Z", "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": "Tue, 09 Dec 2025 18:13:12 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26332-9", "id": "LN:LA26332-9", "label": "Likely Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "0e7e4644-f85d-408c-9ff6-97a3442c196e", "variant": { "@id": "https://reg.genome.network/allele/CA415256307", "id": "CAR:CA415256307", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000252.3:c.690G>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000252.3(MTM1):c.690G>T (p.Trp230Cys)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-02T08:45:10.144Z" } }, "status": { "code": 200, "name": "OK" } }