{ "data": { "@context": "https://genboree.org/evrepo/api/context", "@id": "https://genboree.org/evrepo/api/summary/classification/a3d224b9-8dd7-4ecd-838b-ea908cb7530b/doc/sepio/version/3.1.1", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/135637588", "label": "ClinGen Mitochondrial Disease Nuclear and Mitochondrial Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1_mtDNA", "type": "VariantPathogenicityInterpretationGuideline", "version": "1.0.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0044970", "id": "MONDO:0044970", "label": "mitochondrial disease", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA270779/MONDO:0044970/015/el/0/1678", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA270779/MONDO:0044970/015/ei/1/1679", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50027_EP162093598185344", "id": "CG-PCER-AGENT:CG_50027_EP162093598185344", "type": "Agent" }, "contributionDate": { "date": "2024/3/19", "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://genboree.org/evrepo/api/interpretation/CA270779/MONDO:0044970/015/el/0/1678/1680", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA270779/MONDO:0044970/015/ci/CA270779/MONDO:0044970/015.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50027_EP162093598185344", "id": "CG-PCER-AGENT:CG_50027_EP162093598185344", "type": "Agent" }, "comments": "This variant segregated with disease features in this family as her healthy mother had the variant present 1% in blood, however this does not meet criteria to apply PP1_supporting (at least two segregations). 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", "contributionDate": { "date": "2024/3/19", "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": "CA270779/MONDO:0044970/015/ci/CA270779/MONDO:0044970/015.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA270779/MONDO:0044970/015/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA270779/MONDO:0044970/015/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA270779/MONDO:0044970/015/0/1747", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA270779/MONDO:0044970/015/el/0/1633", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA270779/MONDO:0044970/015/ei/1/1634", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50027_EP162093598185344", "id": "CG-PCER-AGENT:CG_50027_EP162093598185344", "type": "Agent" }, "contributionDate": { "date": "2024/3/19", "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://genboree.org/evrepo/api/interpretation/CA270779/MONDO:0044970/015/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA270779/MONDO:0044970/015/ci/CA270779/MONDO:0044970/015.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50027_EP162093598185344", "id": "CG-PCER-AGENT:CG_50027_EP162093598185344", "type": "Agent" }, "comments": "Complex I deficiency was noted in muscle, and exome sequencing was performed in the proband, her parents, and three healthy siblings ruling out other known genetic etiologies (PMID: 25118196; PP4). ", "contributionDate": { "date": "2024/3/19", "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": "CA270779/MONDO:0044970/015/ci/CA270779/MONDO:0044970/015.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA270779/MONDO:0044970/015/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA270779/MONDO:0044970/015/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA270779/MONDO:0044970/015/0/1633", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA270779/MONDO:0044970/015/el/0/1636", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA270779/MONDO:0044970/015/ei/1/1637", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50027_EP162093598185344", "id": "CG-PCER-AGENT:CG_50027_EP162093598185344", "type": "Agent" }, "contributionDate": { "date": "2024/3/19", "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://genboree.org/evrepo/api/interpretation/CA270779/MONDO:0044970/015/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA270779/MONDO:0044970/015/ci/CA270779/MONDO:0044970/015.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50027_EP162093598185344", "id": "CG-PCER-AGENT:CG_50027_EP162093598185344", "type": "Agent" }, "comments": "This variant is absent in the GenBank dataset, Helix dataset, and gnomAD v3.1.2 (PM2_supporting). 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", "contributionDate": { "date": "2024/3/19", "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": "CA270779/MONDO:0044970/015/ci/CA270779/MONDO:0044970/015.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA270779/MONDO:0044970/015/0/1684/1686", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA270779/MONDO:0044970/015/1/1685", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA270779/MONDO:0044970/015/0/1684", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA270779/MONDO:0044970/015/el/0/1828", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA270779/MONDO:0044970/015/ei/1/1829", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50027_EP162093598185344", "id": "CG-PCER-AGENT:CG_50027_EP162093598185344", "type": "Agent" }, "contributionDate": { "date": "2024/3/19", "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://genboree.org/evrepo/api/interpretation/CA270779/MONDO:0044970/015/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA270779/MONDO:0044970/015/ci/CA270779/MONDO:0044970/015.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50027_EP162093598185344", "id": "CG-PCER-AGENT:CG_50027_EP162093598185344", "type": "Agent" }, "comments": " There are no cybrids, single fiber studies, or other functional assays reported on this variant. ", "contributionDate": { "date": "2024/3/19", "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": "CA270779/MONDO:0044970/015/ci/CA270779/MONDO:0044970/015.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA270779/MONDO:0044970/015/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA270779/MONDO:0044970/015/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA270779/MONDO:0044970/015/0/1828", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA270779/MONDO:0044970/015/el/0/1735", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA270779/MONDO:0044970/015/ei/1/1736", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50027_EP162093598185344", "id": "CG-PCER-AGENT:CG_50027_EP162093598185344", "type": "Agent" }, "contributionDate": { "date": "2024/3/19", "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://genboree.org/evrepo/api/interpretation/CA270779/MONDO:0044970/015/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA270779/MONDO:0044970/015/ci/CA270779/MONDO:0044970/015.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50027_EP162093598185344", "id": "CG-PCER-AGENT:CG_50027_EP162093598185344", "type": "Agent" }, "comments": "The m.10134C>A (p.Q26K) variant in MT-ND3 has been reported in one individual to date, in a girl with Leigh syndrome spectrum disorder (PMID: 25118196). She was reportedly slower than her siblings in reaching motor milestones and at 4-years-old lost the ability to jump, developed an abnormal gait, and had speech difficulty. At 4.5-years-old, she developed worsening speech, mobility, balance, and behaviors after undergoing anesthesia. Brain MRI performed at this time showed extensive signal abnormality involving putamen, globus pallidus bilaterally, and the cerebral peduncles, and brain MRS showed elevated lactate in the basal ganglia. Blood and cerebrospinal fluid (CSF) lactates were normal. Muscle biopsy showed fat accumulation and slightly increased subsarcolemmal mitochondrial aggregates. Liver biopsy showed increased glycogen content and mild biliary ductular proliferation, and electron microscopy showed occasional moderately enlarged mitochondria with paracrystalline and crystalline inclusions. The variant was present at homoplasmy in blood, fibroblasts, liver, and muscle. As this is the only case reported to date, PS4 could not be applied. ", "contributionDate": { "date": "2024/3/19", "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": "CA270779/MONDO:0044970/015/ci/CA270779/MONDO:0044970/015.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA270779/MONDO:0044970/015/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA270779/MONDO:0044970/015/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA270779/MONDO:0044970/015/0/1735", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA270779/MONDO:0044970/015", "metadata": { "created": "2024-12-13T20:17:24.235Z", "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": "Fri, 13 Dec 2024 20:17:24 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "3.1.1" }, "statementOutcome": { "@id": "https://loinc.org/LA26333-7", "id": "LN:LA26333-7", "label": "Uncertain Significance" }, "type": "VariantPathogenicityInterpretation", "uuid": "a3d224b9-8dd7-4ecd-838b-ea908cb7530b", "variant": { "@id": "https://reg.genome.network/allele/CA270779", "id": "CAR:CA270779", "relatedContextualAllele": [ { "alleleName": [ { "name": "NC_012920.1:m.10134C>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NC_012920.1:m.10134C>A" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://genboree.org/evrepo/api/summarysrvc", "when": "2026-04-15T11:54:53.385Z" } }, "status": { "code": 200, "name": "OK" } }