{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/ce020df2-3589-49b1-989b-f1f494f3e1b3/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/135637573", "label": "ClinGen Familial Hypercholesterolemia Expert Panel Specifications to the ACMG/AMP Variant Classification Guidelines Version 1.2", "type": "VariantPathogenicityInterpretationGuideline", "url": "https://clinicalgenome.org/docs/clingen-familial-hypercholesterolemia-expert-panel-specifications-to-the-acmg-amp-variant-interpretation-guidelines-version-1-2/", "version": "1.2.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0007750", "id": "MONDO:0007750", "label": "hypercholesterolemia, familial", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/el/0/1615", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/ei/1/1616", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "contributionDate": { "date": "2026/1/28", "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/CA023430/MONDO:0007750/013/el/0/1615/1617", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "comments": "Variant meets PM2 but is not located in exon 4 or alters a cysteine residue, so PM1 is Not Met.", "contributionDate": { "date": "2026/1/28", "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": "CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1615/1617", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/1/1616", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1615", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/el/0/1678", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/ei/1/1679", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "contributionDate": { "date": "2026/1/28", "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/CA023430/MONDO:0007750/013/el/0/1678/1680", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "comments": "Variant segregates with FH phenotype in at least 4 informative meiosis (minimum 2) from 1 family from Cardiovascular Genetics Laboratory (PathWest Laboratory Medicine WA): 1 affected family member has the variant and 3 non-affected family members do not have the variant, so PP1 is met.", "contributionDate": { "date": "2026/1/28", "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": "CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1678/1680", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/1/1679", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1678", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "contributionDate": { "date": "2026/1/28", "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/CA023430/MONDO:0007750/013/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "comments": "REVEL = 0.755. It is above 0.75, so PP3 is met.", "contributionDate": { "date": "2026/1/28", "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": "CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/ei/1/1634", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "contributionDate": { "date": "2026/1/28", "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/CA023430/MONDO:0007750/013/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "comments": "Variant meets PM2 and is identified in at least 7 index cases who fulfill criteria for FH from different labs (1 case with DLCN criteria>=6 from CMG UZA, Belgium; 1 index case with Dutch lipid clinic network >=6 from Research Lab of Molecular Genetics of Lipid Metabolism - Department of Translational and Precision Medicine, Italy; 1 index case with Dutch lipid clinic network >=6 from Service de Biochimie et de Biologie Moléculaire, Hospices Civils de Lyon, Lyon, France; 1 index case with Dutch lipid clinic network >=6 from Cardiovascular Genetics Laboratory (PathWest Laboratory Medicine WA), Australia; at least 1 index case (0.6% in 169) who fulfills MEDPED criteria for FH from Greece (PMID: 21925044); at least 1 index case with diagnosed with definite heterozygous FH from The Netherlands (PMID: 16250003); 1 index case with Taiwan Lipids Guideline criteria for FH from Taiwan (33994402)), after alternative causes of high cholesterol were excluded so PP4 is met.\n", "contributionDate": { "date": "2026/1/28", "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": "CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/el/0/1702", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/ei/1/1703", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "contributionDate": { "date": "2026/1/28", "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/CA023430/MONDO:0007750/013/el/0/1702/1704", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "comments": "Case-control data not reported, so BS2 is Not Met.", "contributionDate": { "date": "2026/1/28", "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": "CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1702/1704", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/1/1703", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1702", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/ei/1/1718", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "contributionDate": { "date": "2026/1/28", "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/CA023430/MONDO:0007750/013/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "comments": "Variant meets PM2 and is identified in an index case with homozygous FH phenotype (LDL>500mg/dL) and LDLR variant c.2475C>A/p.(Asn825Lys), classified as Pathogenic by these guidelines, in trans, from Spain (PMID: 27784735), so PM3 is met.", "contributionDate": { "date": "2026/1/28", "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": "CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/ei/1/1781", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "contributionDate": { "date": "2026/1/28", "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/CA023430/MONDO:0007750/013/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "comments": "3 other missense variants in the same codon:\n- NM_000527.5(LDLR):c.1195G>T (p.Ala399Ser) (ClinVar ID 440632)\n \t- Uncertain significance by these guidelines\n- NM_000527.5(LDLR):c.1196C>A (p.Ala399Asp) (ClinVar ID 226350)\n - Likely pathogenic by these guidelines\n- NM_000527.5(LDLR):c.1196C>T (p.Ala399Val) (ClinVar ID 3074081)\n - Uncertain significance by these guidelines\nThere is no variant in the same codon classified as Pathogenic by these guidelines, so PM5 is not met.\n", "contributionDate": { "date": "2026/1/28", "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": "CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1780", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/el/0/1591", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/ei/1/1592", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "contributionDate": { "date": "2026/1/28", "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/CA023430/MONDO:0007750/013/el/0/1591/1593", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "comments": "Variant meets PM2 and is missense, so PM4 is Not Met.", "contributionDate": { "date": "2026/1/28", "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": "CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1591/1593", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/1/1592", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1591", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/el/0/1765", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/ei/1/1766", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "contributionDate": { "date": "2026/1/28", "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/CA023430/MONDO:0007750/013/el/0/1765/1767", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "comments": "No more missense variants that lead to the same amino acid change, so PS1 is Not Met.", "contributionDate": { "date": "2026/1/28", "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": "CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1765/1767", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/1/1766", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1765", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/el/0/1663", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/ei/1/1664", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "contributionDate": { "date": "2026/1/28", "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/CA023430/MONDO:0007750/013/el/0/1663/1665", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "comments": "de novo occurrence data not reported, so PS2 is Not Met.", "contributionDate": { "date": "2026/1/28", "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": "CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1663/1665", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/1/1664", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1663", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/ei/1/1829", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "contributionDate": { "date": "2026/1/28", "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/CA023430/MONDO:0007750/013/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA023430/MONDO:0007750/013/ci/EV000001963", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "comments": "83% cell surface LDLR, 95% binding and 92% uptake in Heterologous cells (CHO), FACS assays", "contributionDate": { "date": "2026/1/28", "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": "CA023430/MONDO:0007750/013/ci/EV000001963", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/32015373", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1828", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/el/0/1699", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/ei/1/1700", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "contributionDate": { "date": "2026/1/28", "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/CA023430/MONDO:0007750/013/el/0/1699/1701", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "comments": "Variant meets PM2 and is identified in at least 7 index cases who fulfill criteria for FH from different labs (1 case with DLCN criteria>=6 from CMG UZA, Belgium; 1 index case with Dutch lipid clinic network >=6 from Research Lab of Molecular Genetics of Lipid Metabolism - Department of Translational and Precision Medicine, Italy; 1 index case with Dutch lipid clinic network >=6 from Service de Biochimie et de Biologie Moléculaire, Hospices Civils de Lyon, Lyon, France; 1 index case with Dutch lipid clinic network >=6 from Cardiovascular Genetics Laboratory (PathWest Laboratory Medicine WA), Australia; at least 1 index case (0.6% in 169) who fulfills MEDPED criteria for FH from Greece (PMID: 21925044); at least 1 index case with diagnosed with definite heterozygous FH from The Netherlands (PMID: 16250003); 1 index case with Taiwan Lipids Guideline criteria for FH from Taiwan (33994402)), so PS4_Moderate is met.\n", "contributionDate": { "date": "2026/1/28", "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": "CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1699/1701", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/1/1700", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1699", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/el/0/1684", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/ei/1/1685", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "contributionDate": { "date": "2026/1/28", "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/CA023430/MONDO:0007750/013/el/0/1684/1686", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "comments": "REVEL = 0.755. It is not below 0.50, so BP4 is Not Met.", "contributionDate": { "date": "2026/1/28", "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": "CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1684/1686", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/1/1685", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1684", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/el/0/1597", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/ei/1/1598", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "contributionDate": { "date": "2026/1/28", "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/CA023430/MONDO:0007750/013/el/0/1597/1599", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "comments": "index case also has APOB c.2789A>G with LDL-C 224 mg/dL, but phase is unknown, so BP2 is not met.", "contributionDate": { "date": "2026/1/28", "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": "CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1597/1599", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/1/1598", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1597", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/el/0/1777", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/ei/1/1778", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "contributionDate": { "date": "2026/1/28", "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/CA023430/MONDO:0007750/013/el/0/1777/1779", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "comments": "PopMax MAF = 0.0000093 (0.00093%) in European non Finnish exomes (gnomAD v4.1), so BA1 is not met.", "contributionDate": { "date": "2026/1/28", "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": "CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1777/1779", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/1/1778", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1777", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/el/0/1672", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/ei/1/1673", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "contributionDate": { "date": "2026/1/28", "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/CA023430/MONDO:0007750/013/el/0/1672/1674", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "comments": "de novo occurrence data not reported, so PM6 is Not Met.", "contributionDate": { "date": "2026/1/28", "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": "CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1672/1674", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/1/1673", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1672", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/el/0/1798", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/ei/1/1799", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "contributionDate": { "date": "2026/1/28", "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/CA023430/MONDO:0007750/013/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "comments": "PopMax MAF = 0.0000093 (0.00093%) in European non Finnish exomes+genomes (gnomAD v4.1), so PM2 is Met.", "contributionDate": { "date": "2026/1/28", "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": "CA023430/MONDO:0007750/013/ci/CA023430/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1798/1800", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/1/1799", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1798", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/el/0/1594", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/ei/1/1595", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "contributionDate": { "date": "2026/1/28", "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/CA023430/MONDO:0007750/013/el/0/1594/1596", "evidenceItem": [ { "@id": 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"https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1594", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/el/0/1804", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/ei/1/1805", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "contributionDate": { "date": "2026/1/28", "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/CA023430/MONDO:0007750/013/el/0/1804/1806", "evidenceItem": [ { "@id": 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"@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1588", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/el/0/1654", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA023430/MONDO:0007750/013/ei/1/1655", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50004_EP162454503244642", "id": "CG-PCER-AGENT:CG_50004_EP162454503244642", "type": "Agent" }, "contributionDate": { "date": "2026/1/28", "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": 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"statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013/0/1654", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA023430/MONDO:0007750/013", "metadata": { "created": "2026-01-28T03:39:13.950Z", "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": "Wed, 28 Jan 2026 03:39:13 -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": "ce020df2-3589-49b1-989b-f1f494f3e1b3", "variant": { "@id": "https://reg.genome.network/allele/CA023430", "id": "CAR:CA023430", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000527.5:c.1195G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000527.5(LDLR):c.1195G>A (p.Ala399Thr)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-27T11:57:54.222Z" } }, "status": { "code": 200, "name": "OK" } }