{ "data": [ { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/70e55828-a26c-447c-863d-156419f819e2/doc/sepio/version/2.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/643243110", "label": "ClinGen RASopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RAF1 Version 2.3.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "2.3.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0021060", "id": "MONDO:0021060", "label": "RASopathy", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA261617/MONDO:0021060/040/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA261617/MONDO:0021060/040/ei/1/1736", "contribution": [ { "agent": { "@id": 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"https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2025/3/25", "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/CA261617/MONDO:0021060/040/el/0/1615/1617", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA261617/MONDO:0021060/040/ci/EV000000212", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "Furthermore, the variant is in a location that has been defined by the ClinGen RASopathy Expert Panel to be a mutational hotspot or domain of RAF1 (PM1; PMID 29493581).", "contributionDate": { "date": "2025/3/25", "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": "CA261617/MONDO:0021060/040/ci/EV000000212", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/29493581", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/040/0/1615/1617", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/040/1/1616", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/040/0/1615", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/040", "metadata": { "created": "2025-04-01T16:27:30.751Z", "note": "DISCLAIMER: While the data/content in this document is approved by ClinGen expert panel(s), the SEPIO schema presented here is an initial prototype and has not been reviewed nor finalized by the ClinGen Data Exchange Modeling Team. We expect it to differ significantly from the final schema.", "producedAtUTC": "Tue, 01 Apr 2025 16:27:30 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "2.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA6668-3", "id": "LN:LA6668-3", "label": "Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "70e55828-a26c-447c-863d-156419f819e2", "variant": { "@id": "https://reg.genome.network/allele/CA261617", "id": "CAR:CA261617", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_002880.4:c.775T>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_002880.4(RAF1):c.775T>A (p.Ser259Thr)" } ], "type": "CAR" } }, { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/70e55828-a26c-447c-863d-156419f819e2/doc/sepio/version/1.0.0", "assertionMethod": { "type": "VariantPathogenicityInterpretationGuideline" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0021060", "id": "MONDO:0021060", "label": "RASopathy", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA261617/MONDO:0021060/004/el/0/1615", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA261617/MONDO:0021060/004/ei/1/1616", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2020/4/13", "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/CA261617/MONDO:0021060/004/el/0/1615/1617", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA261617/MONDO:0021060/004/ci/EV000000212", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "Furthermore, the variant is in a location that has been defined by the ClinGen RASopathy Expert Panel to be a mutational hotspot or domain of RAF1 (PM1; PMID 29493581).", "contributionDate": { "date": "2020/4/13", "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": "CA261617/MONDO:0021060/004/ci/EV000000212", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/29493581", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004/0/1615/1617", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004/1/1616", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004/0/1615", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA261617/MONDO:0021060/004/el/0/1798", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA261617/MONDO:0021060/004/ei/1/1799", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2020/4/13", "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/0011", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "0011", "label": "PM2", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA261617/MONDO:0021060/004/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA261617/MONDO:0021060/004/ci/CA261617/MONDO:0021060/004.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2020/4/13", "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": "CA261617/MONDO:0021060/004/ci/CA261617/MONDO:0021060/004.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004/0/1798/1800", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004/1/1799", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004/0/1798", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA261617/MONDO:0021060/004/el/0/1678", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA261617/MONDO:0021060/004/ei/1/1679", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2020/4/13", "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/0060", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0060", "label": "PP1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA261617/MONDO:0021060/004/el/0/1678/1680", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA261617/MONDO:0021060/004/ci/CA261617/MONDO:0021060/004.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "The p.Ser259Thr variant in RAF1 has been reported to segregate with clinical features of a RASopathy in at least 3 family members (PP1; GeneDx, Zenker et al. internal data; ClinVar SCV000209017.9).", "contributionDate": { "date": "2020/4/13", "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": "CA261617/MONDO:0021060/004/ci/CA261617/MONDO:0021060/004.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004/0/1678/1680", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004/1/1679", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004/0/1678", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA261617/MONDO:0021060/004/el/0/1837", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA261617/MONDO:0021060/004/ei/1/1838", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2020/4/13", "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/0061", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0061", "label": "PP2", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA261617/MONDO:0021060/004/el/0/1837/1839", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA261617/MONDO:0021060/004/ci/CA261617/MONDO:0021060/004.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "The variant is located in the RAF1 gene, which has been defined by the ClinGen RASopathy Expert Panel as a gene with a low rate of benign missense variants and pathogenic missense variants are common (PP2; PMID: 29493581).", "contributionDate": { "date": "2020/4/13", "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": "CA261617/MONDO:0021060/004/ci/CA261617/MONDO:0021060/004.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004/0/1837/1839", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004/1/1838", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004/0/1837", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA261617/MONDO:0021060/004/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA261617/MONDO:0021060/004/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2020/4/13", "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/CA261617/MONDO:0021060/004/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA261617/MONDO:0021060/004/ci/CA261617/MONDO:0021060/004.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2020/4/13", "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": "CA261617/MONDO:0021060/004/ci/CA261617/MONDO:0021060/004.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA261617/MONDO:0021060/004/el/0/1606", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA261617/MONDO:0021060/004/ei/1/1607", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2020/4/13", "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/0032", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0032", "label": "PS4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA261617/MONDO:0021060/004/el/0/1606/1608", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA261617/MONDO:0021060/004/ci/CA261617/MONDO:0021060/004.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "The p.Ser259Thr variant has been identified in at least 8 independent occurrences in patients with a RASopathy (PS4_Supporting; GeneDx, Partners LMM, Institute of Human Genetics, Otto von Guericke University Magdeburg internal data; GTR ID's: 26957, 21766, 506381 PMID: 21784453; ClinVar SCV000061360.5; SCV000209017.10).", "contributionDate": { "date": "2020/4/13", "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": "CA261617/MONDO:0021060/004/ci/CA261617/MONDO:0021060/004.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004/0/1606/1608", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004/1/1607", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004/0/1606", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA261617/MONDO:0021060/004/el/0/1729", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA261617/MONDO:0021060/004/ei/1/1730", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2020/4/13", "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/0037", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0037", "label": "PM6", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA261617/MONDO:0021060/004/el/0/1729/1731", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA261617/MONDO:0021060/004/ci/CA261617/MONDO:0021060/004.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "The c.775T>A (p.Ser259Thr) variant in RAF1 has been reported in the literature in at least 2 unconfirmed de novo occurrences in patients with clinical features of a RASopathy (PM6_Strong; APHP-Robert Debré Hospital internal data; GTR ID's: 28338).", "contributionDate": { "date": "2020/4/13", "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": "CA261617/MONDO:0021060/004/ci/CA261617/MONDO:0021060/004.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004/0/1729/1731", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004/1/1730", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004/0/1729", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA261617/MONDO:0021060/004/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA261617/MONDO:0021060/004/ei/1/1829", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2020/4/13", "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/0052", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0052", "label": "PS3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA261617/MONDO:0021060/004/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA261617/MONDO:0021060/004/ci/CA261617/MONDO:0021060/004.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "In vitro functional studies provide some evidence that the p.Ser259Thr variant may impact protein function (PS3; PMID: 21784453, 20052757).", "contributionDate": { "date": "2020/4/13", "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": "CA261617/MONDO:0021060/004/ci/CA261617/MONDO:0021060/004.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004/0/1828", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA261617/MONDO:0021060/004/el/0/1621", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA261617/MONDO:0021060/004/ei/1/1622", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "contributionDate": { "date": "2020/4/13", "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/0056", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0056", "label": "PM5", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA261617/MONDO:0021060/004/el/0/1621/1623", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA261617/MONDO:0021060/004/ci/CA261617/MONDO:0021060/004.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50021_EP155190663717081", "id": "CG-PCER-AGENT:CG_50021_EP155190663717081", "type": "Agent" }, "comments": "At least 2 other pathogenic missense variants have been previously identified at this codon of RAF1 which may indicate that this residue is critical to the function of the protein (PM5_Strong; ClinVar 40603, 40602, 228288).", "contributionDate": { "date": "2020/4/13", "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": "CA261617/MONDO:0021060/004/ci/CA261617/MONDO:0021060/004.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004/0/1621/1623", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004/1/1622", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004/0/1621", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA261617/MONDO:0021060/004", "metadata": { "created": "2024-09-27T20:42:48.541Z", "note": "DISCLAIMER: While the data/content in this document is approved by ClinGen expert panel(s), the SEPIO schema presented here is an initial prototype and has not been reviewed nor finalized by the ClinGen Data Exchange Modeling Team. We expect it to differ significantly from the final schema.", "producedAtUTC": "Fri, 27 Sep 2024 20:42:48 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA6668-3", "id": "LN:LA6668-3", "label": "Pathogenic" }, "type": "VariantPathogenicityInterpretation", "uuid": "70e55828-a26c-447c-863d-156419f819e2", "variant": { "@id": "https://reg.genome.network/allele/CA261617", "id": "CAR:CA261617", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_002880.3:c.775T>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_002880.3(RAF1):c.775T>A (p.Ser259Thr)" } ], "type": "CAR" } } ], "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-11T17:04:02.292Z" } }, "status": { "code": 200, "name": "OK" } }