{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/b81fb118-4d2b-4441-8fe1-db5668f18578/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/CA10576301/MONDO:0007750/013/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/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/CA10576301/MONDO:0007750/013/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10576301/MONDO:0007750/013/ci/CA10576301/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 = 0.82. 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": "CA10576301/MONDO:0007750/013/ci/CA10576301/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/MONDO:0007750/013/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/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/CA10576301/MONDO:0007750/013/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10576301/MONDO:0007750/013/ci/CA10576301/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 3 unrelated index cases who fulfill criteria for FH from different labs (2 unrelated index cases, both with Dutch lipid clinic network >=6; at least 1 index case who fulfills DLCN>9 criteria for FH (definite FH) from The Netherlands (PMID: 11810272)), after alternative causes of high cholesterol were excluded so PP4 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": "CA10576301/MONDO:0007750/013/ci/CA10576301/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/MONDO:0007750/013/el/0/1702", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/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/CA10576301/MONDO:0007750/013/el/0/1702/1704", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10576301/MONDO:0007750/013/ci/CA10576301/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": "CA10576301/MONDO:0007750/013/ci/CA10576301/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1702/1704", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/1/1703", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1702", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/MONDO:0007750/013/el/0/1648", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/MONDO:0007750/013/ei/1/1649", "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/CA10576301/MONDO:0007750/013/el/0/1648/1650", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10576301/MONDO:0007750/013/ci/CA10576301/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 6 informative meioses (minimum 6) from 2 families from Cardiovascular Genetics Laboratory (PathWest Laboratory Medicine WA): 5 affected family members have the variant and 1 non-affected family member does not have the variant, so PP1_Strong 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": "CA10576301/MONDO:0007750/013/ci/CA10576301/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1648/1650", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/1/1649", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1648", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/MONDO:0007750/013/el/0/1684", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/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/CA10576301/MONDO:0007750/013/el/0/1684/1686", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10576301/MONDO:0007750/013/ci/CA10576301/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 = 0.82. 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": "CA10576301/MONDO:0007750/013/ci/CA10576301/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1684/1686", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/1/1685", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1684", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/MONDO:0007750/013/el/0/1597", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/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/CA10576301/MONDO:0007750/013/el/0/1597/1599", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10576301/MONDO:0007750/013/ci/CA10576301/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": "Not observed in trans with other LP/P variants, 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": "CA10576301/MONDO:0007750/013/ci/CA10576301/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1597/1599", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/1/1598", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1597", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/MONDO:0007750/013/el/0/1777", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/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/CA10576301/MONDO:0007750/013/el/0/1777/1779", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10576301/MONDO:0007750/013/ci/CA10576301/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 = 0.000003390 (0.0003390%) in European non Finnish exomes+genomes (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": "CA10576301/MONDO:0007750/013/ci/CA10576301/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1777/1779", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/1/1778", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1777", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/MONDO:0007750/013/el/0/1765", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/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/CA10576301/MONDO:0007750/013/el/0/1765/1767", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10576301/MONDO:0007750/013/ci/CA10576301/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": "CA10576301/MONDO:0007750/013/ci/CA10576301/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1765/1767", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/1/1766", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1765", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/MONDO:0007750/013/el/0/1663", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/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/CA10576301/MONDO:0007750/013/el/0/1663/1665", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10576301/MONDO:0007750/013/ci/CA10576301/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": "CA10576301/MONDO:0007750/013/ci/CA10576301/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1663/1665", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/1/1664", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1663", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/MONDO:0007750/013/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/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/CA10576301/MONDO:0007750/013/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10576301/MONDO:0007750/013/ci/CA10576301/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": "There are no functional studies reported for this variant, so PS3 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": "CA10576301/MONDO:0007750/013/ci/CA10576301/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1828", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/MONDO:0007750/013/el/0/1615", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/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/CA10576301/MONDO:0007750/013/el/0/1615/1617", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10576301/MONDO:0007750/013/ci/CA10576301/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": "CA10576301/MONDO:0007750/013/ci/CA10576301/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1615/1617", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/1/1616", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1615", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/MONDO:0007750/013/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/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/CA10576301/MONDO:0007750/013/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10576301/MONDO:0007750/013/ci/CA10576301/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": "Not observed in trans with other LP/P variants, so PM3 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": "CA10576301/MONDO:0007750/013/ci/CA10576301/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/MONDO:0007750/013/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/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/CA10576301/MONDO:0007750/013/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10576301/MONDO:0007750/013/ci/CA10576301/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>A (p.Ala399Thr) (ClinVar ID 183109)\n \t- Likely pathogenic by these guidelines\n- NM_000527.5(LDLR):c.1195G>T (p.Ala399Ser) (ClinVar ID 440632)\n - Uncertain significance 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.", "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": "CA10576301/MONDO:0007750/013/ci/CA10576301/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1780", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/MONDO:0007750/013/el/0/1591", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/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/CA10576301/MONDO:0007750/013/el/0/1591/1593", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10576301/MONDO:0007750/013/ci/CA10576301/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": "CA10576301/MONDO:0007750/013/ci/CA10576301/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1591/1593", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/1/1592", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1591", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/MONDO:0007750/013/el/0/1672", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/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/CA10576301/MONDO:0007750/013/el/0/1672/1674", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10576301/MONDO:0007750/013/ci/CA10576301/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": "CA10576301/MONDO:0007750/013/ci/CA10576301/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1672/1674", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/1/1673", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1672", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/MONDO:0007750/013/el/0/1798", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/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/CA10576301/MONDO:0007750/013/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10576301/MONDO:0007750/013/ci/CA10576301/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 = 0.000003390 (0.0003390%) 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": "CA10576301/MONDO:0007750/013/ci/CA10576301/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1798/1800", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/1/1799", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1798", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/MONDO:0007750/013/el/0/1594", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/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/CA10576301/MONDO:0007750/013/el/0/1594/1596", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10576301/MONDO:0007750/013/ci/CA10576301/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 is missense, so PVS1 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": "CA10576301/MONDO:0007750/013/ci/CA10576301/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1594/1596", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/1/1595", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1594", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/MONDO:0007750/013/el/0/1804", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/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/CA10576301/MONDO:0007750/013/el/0/1804/1806", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10576301/MONDO:0007750/013/ci/CA10576301/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 = 0.000003390 (0.0003390%) in European non Finnish exomes+genomes (gnomAD v4.1), so BS1 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": "CA10576301/MONDO:0007750/013/ci/CA10576301/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1804/1806", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/1/1805", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1804", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/MONDO:0007750/013/el/0/1768", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/MONDO:0007750/013/ei/1/1769", "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/CA10576301/MONDO:0007750/013/el/0/1768/1770", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10576301/MONDO:0007750/013/ci/CA10576301/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": "Lack of segregation data not reported, so BS4 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": "CA10576301/MONDO:0007750/013/ci/CA10576301/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1768/1770", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/1/1769", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1768", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/MONDO:0007750/013/el/0/1588", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/MONDO:0007750/013/ei/1/1589", "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/CA10576301/MONDO:0007750/013/el/0/1588/1590", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10576301/MONDO:0007750/013/ci/CA10576301/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": "There are no functional studies reported for this variant, so BS3 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": "CA10576301/MONDO:0007750/013/ci/CA10576301/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1588/1590", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/1/1589", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1588", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/MONDO:0007750/013/el/0/1654", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/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": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/MONDO:0007750/013/el/0/1654/1656", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10576301/MONDO:0007750/013/ci/CA10576301/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 is not synonymous, so BP7 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": "CA10576301/MONDO:0007750/013/ci/CA10576301/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1654/1656", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/1/1655", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1654", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/MONDO:0007750/013/el/0/1606", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA10576301/MONDO:0007750/013/ei/1/1607", "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/CA10576301/MONDO:0007750/013/el/0/1606/1608", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA10576301/MONDO:0007750/013/ci/CA10576301/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 3 unrelated index cases who fulfill criteria for FH from different labs (2 unrelated index cases, both with Dutch lipid clinic network >=6 from Cardiovascular Genetics Laboratory (PathWest Laboratory Medicine WA); at least 1 index case who fulfills DLCN>9 criteria for FH (definite FH) from The Netherlands (PMID: 11810272)), so PS4_Supporting 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": "CA10576301/MONDO:0007750/013/ci/CA10576301/MONDO:0007750/013.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1606/1608", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/1/1607", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013/0/1606", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA10576301/MONDO:0007750/013", "metadata": { "created": "2026-01-28T04:00:22.076Z", "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 04:00:21 -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": "b81fb118-4d2b-4441-8fe1-db5668f18578", "variant": { "@id": "https://reg.genome.network/allele/CA10576301", "id": "CAR:CA10576301", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000527.5:c.1196C>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000527.5(LDLR):c.1196C>A (p.Ala399Asp)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-28T08:27:43.211Z" } }, "status": { "code": 200, "name": "OK" } }