{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://erepo.genome.network/evrepo/api/summary/classification/05a3bc2c-efbf-4f9f-91c2-b48c53545e2f/doc/sepio/version/1.0.0", "assertionMethod": { "type": "VariantPathogenicityInterpretationGuideline" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0008723", "id": "MONDO:0008723", "label": "very long chain acyl-CoA dehydrogenase deficiency", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA312265/MONDO:0008723/021/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA312265/MONDO:0008723/021/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50048_EP16455509033668", "id": "CG-PCER-AGENT:CG_50048_EP16455509033668", "type": "Agent" }, "contributionDate": { "date": "2022/9/22", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0062", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0062", "label": "PP3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA312265/MONDO:0008723/021/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA312265/MONDO:0008723/021/ci/CA312265/MONDO:0008723/021.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50048_EP16455509033668", "id": "CG-PCER-AGENT:CG_50048_EP16455509033668", "type": "Agent" }, "comments": "ReVEL score of 0.975", "contributionDate": { "date": "2022/9/22", "description": "Date on which this 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"https://erepo.genome.network/evrepo/api//agent/CG_50048_EP16455509033668", "id": "CG-PCER-AGENT:CG_50048_EP16455509033668", "type": "Agent" }, "comments": "Reported this variant in heterozygous with R453Ter, with FAO flux of 0.71 (NL 4.8, thus ~15% of NL).", "contributionDate": { "date": "2022/9/22", "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": "CA312265/MONDO:0008723/021/ci/CA312265/MONDO:0008723/021.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA312265/MONDO:0008723/021/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA312265/MONDO:0008723/021/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA312265/MONDO:0008723/021/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA312265/MONDO:0008723/021/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA312265/MONDO:0008723/021/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50048_EP16455509033668", "id": "CG-PCER-AGENT:CG_50048_EP16455509033668", "type": "Agent" }, "contributionDate": { "date": "2022/9/22", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/0030", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0030", "label": "PM2", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA312265/MONDO:0008723/021/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA312265/MONDO:0008723/021/ci/CA312265/MONDO:0008723/021.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50048_EP16455509033668", "id": "CG-PCER-AGENT:CG_50048_EP16455509033668", "type": "Agent" }, "comments": "gnomad has 8 alleles out of 282884 alleles, highest MAF=0.01% in South Asian population; total MAF=0.003%, < 0.1%", "contributionDate": { "date": "2022/9/22", "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": "CA312265/MONDO:0008723/021/ci/CA312265/MONDO:0008723/021.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA312265/MONDO:0008723/021/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA312265/MONDO:0008723/021/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA312265/MONDO:0008723/021/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA312265/MONDO:0008723/021/el/0/1615", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA312265/MONDO:0008723/021/ei/1/1616", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50048_EP16455509033668", "id": "CG-PCER-AGENT:CG_50048_EP16455509033668", "type": "Agent" }, "contributionDate": { "date": "2022/9/22", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/006", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "006", "label": "PM1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA312265/MONDO:0008723/021/el/0/1615/1617", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA312265/MONDO:0008723/021/ci/EV000001440", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50048_EP16455509033668", "id": "CG-PCER-AGENT:CG_50048_EP16455509033668", "type": "Agent" }, "comments": "CpG dinucleotides in the codon for arginine326 is a hot spot.", "contributionDate": { "date": "2022/9/22", "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": "CA312265/MONDO:0008723/021/ci/EV000001440", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/9973285", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA312265/MONDO:0008723/021/ci/EV000001430", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50048_EP16455509033668", "id": "CG-PCER-AGENT:CG_50048_EP16455509033668", "type": "Agent" }, "comments": "Arginine coordinates FAD nucleotide binding. Mutation would be disruptive.", "contributionDate": { "date": "2022/9/22", "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": "CA312265/MONDO:0008723/021/ci/EV000001430", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/20060901", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA312265/MONDO:0008723/021/0/1615/1617", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA312265/MONDO:0008723/021/1/1616", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA312265/MONDO:0008723/021/0/1615", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA312265/MONDO:0008723/021/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA312265/MONDO:0008723/021/ei/1/1718", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50048_EP16455509033668", "id": "CG-PCER-AGENT:CG_50048_EP16455509033668", "type": "Agent" }, "contributionDate": { "date": "2022/9/22", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/007", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "007", "label": "PM3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA312265/MONDO:0008723/021/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA312265/MONDO:0008723/021/ci/CA312265/MONDO:0008723/021.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50048_EP16455509033668", "id": "CG-PCER-AGENT:CG_50048_EP16455509033668", "type": "Agent" }, "comments": "This variant was reported unconfirmed in compound heterozygous with R453Ter with 15% of normal FAO flux (PMID 20060901) and another unconfirmed in compound heterozygous with V283A with abnormal NBS (PMID 27246109).\n\nReported with frameshift mutation in 'patient 3' with VLCADD. Phase not determined. ", "contributionDate": { "date": "2022/9/22", "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": "CA312265/MONDO:0008723/021/ci/CA312265/MONDO:0008723/021.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA312265/MONDO:0008723/021/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA312265/MONDO:0008723/021/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA312265/MONDO:0008723/021/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA312265/MONDO:0008723/021/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA312265/MONDO:0008723/021/ei/1/1781", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50048_EP16455509033668", "id": "CG-PCER-AGENT:CG_50048_EP16455509033668", "type": "Agent" }, "contributionDate": { "date": "2022/9/22", "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" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/008", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "008", "label": "PM5", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA312265/MONDO:0008723/021/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA312265/MONDO:0008723/021/ci/CA312265/MONDO:0008723/021.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50048_EP16455509033668", "id": "CG-PCER-AGENT:CG_50048_EP16455509033668", "type": "Agent" }, "comments": "R366C is an alternative change. May classify likely pathogenic with same criteria applied here. In that case it would be PM5_supporting, still not enough to push to R366H to pathogenic. ", "contributionDate": { "date": "2022/9/22", "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": "CA312265/MONDO:0008723/021/ci/CA312265/MONDO:0008723/021.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA312265/MONDO:0008723/021/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA312265/MONDO:0008723/021/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA312265/MONDO:0008723/021/0/1780", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA312265/MONDO:0008723/021", "metadata": { "created": "2024-09-28T00:35:42.191Z", "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": "Sat, 28 Sep 2024 00:35:42 -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": "05a3bc2c-efbf-4f9f-91c2-b48c53545e2f", "variant": { "@id": "https://reg.genome.network/allele/CA312265", "id": "CAR:CA312265", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000018.4:c.1097G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000018.4(ACADVL):c.1097G>A (p.Arg366His)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-05-11T15:53:30.904Z" } }, "status": { "code": 200, "name": "OK" } }