{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://erepo.genome.network/evrepo/api/summary/classification/2eaf4e3c-85c2-49cd-8343-42a8a9e94d1b/doc/sepio/version/1.0.0", "assertionMethod": { "type": "VariantPathogenicityInterpretationGuideline" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0009861", "id": "MONDO:0009861", "label": "phenylketonuria", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229668/MONDO:0009861/006/el/0/1696", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229668/MONDO:0009861/006/ei/1/1697", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "contributionDate": { "date": "2021/9/6", "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/0045", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0045", "label": "PS3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229668/MONDO:0009861/006/el/0/1696/1698", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA229668/MONDO:0009861/006/ci/EV000000078", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "Investigated 8 variants, including c.635T>C (p.L212P). We used an in vitro expression system in combination with liquid chromatography (LC) applied with electrospray ionization tandem mass spectrometry (ESI-MS-MS) for the quantification of tyrosine (Tyr) produced from phenylalanine (Phe) to assess the residual activities. The residual activity expressed as a percentage of the wild-type enzyme activity, was: 17.0 ± 7.0% (p.L212P). All of the PAH variant proteins with rather low activity (p.L212P, p.R270K and p.R261P) also exhibited reduced amounts of PAH protein, compared to wild-type.", "contributionDate": { "date": "2021/9/6", "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": "CA229668/MONDO:0009861/006/ci/EV000000078", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/27620137", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA229668/MONDO:0009861/006/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA229668/MONDO:0009861/006/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA229668/MONDO:0009861/006/0/1696", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229668/MONDO:0009861/006/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229668/MONDO:0009861/006/ei/1/1748", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "contributionDate": { "date": "2021/9/6", "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/CA229668/MONDO:0009861/006/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA229668/MONDO:0009861/006/ci/CA229668/MONDO:0009861/006.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "Deleterious in SIFT, Polyphen2, MutationTaster", "contributionDate": { "date": "2021/9/6", "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": "CA229668/MONDO:0009861/006/ci/CA229668/MONDO:0009861/006.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA229668/MONDO:0009861/006/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA229668/MONDO:0009861/006/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA229668/MONDO:0009861/006/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229668/MONDO:0009861/006/el/0/1633", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229668/MONDO:0009861/006/ei/1/1634", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "contributionDate": { "date": "2021/9/6", "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/0063", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000329", "id": "SEPIO:0000329", "label": "Pathogenic Supporting" }, "id": "0063", "label": "PP4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229668/MONDO:0009861/006/el/0/1633/1635", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA229668/MONDO:0009861/006/ci/EV000000501", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "We successfully analyzed 135 of 141 chromosomes from phenylketonuria (PKU) probands (95.7% of the sample), and eight additional chromosomes from a small number of probands with non-PKU hyperphenylalaninemia (HPA). L212P found on 0.7% of 135 alleles (1 allele).", "contributionDate": { "date": "2021/9/6", "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": "CA229668/MONDO:0009861/006/ci/EV000000501", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/9781015", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA229668/MONDO:0009861/006/0/1633/1635", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA229668/MONDO:0009861/006/1/1634", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA229668/MONDO:0009861/006/0/1633", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229668/MONDO:0009861/006/el/0/1717", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229668/MONDO:0009861/006/ei/1/1718", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "contributionDate": { "date": "2021/9/6", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/007", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "007", "label": "PM3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229668/MONDO:0009861/006/el/0/1717/1719", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA229668/MONDO:0009861/006/ci/CA229668/MONDO:0009861/006.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "detected with p.R408W(c.1222C>T) parental analysis not reported PMID: 17502162; p.R158Q parental analysis not reported PMID: 23430918; c.1066-11G>A] parental analysis not reported PMID: 26666653", "contributionDate": { "date": "2021/9/6", "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": "CA229668/MONDO:0009861/006/ci/CA229668/MONDO:0009861/006.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA229668/MONDO:0009861/006/0/1717/1719", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA229668/MONDO:0009861/006/1/1718", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA229668/MONDO:0009861/006/0/1717", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229668/MONDO:0009861/006/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229668/MONDO:0009861/006/ei/1/1781", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "contributionDate": { "date": "2021/9/6", "description": "Date on which this evidence was provided" }, "contributionRole": { "@id": "https://obofoundry.org/sepio/0000156", "id": "SEPIO:0000516", "label": "curator role", "type": "ContributoryRole" }, "type": "Contribution" } ], "criterion": { "@id": "https://obofoundry.org/sepio/clingen/008", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "008", "label": "PM5", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229668/MONDO:0009861/006/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA229668/MONDO:0009861/006/ci/CA229668/MONDO:0009861/006.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "The current variant is the only variant found in this codon in ClinVar.", "contributionDate": { "date": "2021/9/6", "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": "CA229668/MONDO:0009861/006/ci/CA229668/MONDO:0009861/006.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA229668/MONDO:0009861/006/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA229668/MONDO:0009861/006/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA229668/MONDO:0009861/006/0/1780", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229668/MONDO:0009861/006/el/0/1798", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA229668/MONDO:0009861/006/ei/1/1799", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "contributionDate": { "date": "2021/9/6", "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/CA229668/MONDO:0009861/006/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA229668/MONDO:0009861/006/ci/CA229668/MONDO:0009861/006.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "Not found in ExAC, gnomAD, 1000G, or ESP", "contributionDate": { "date": "2021/9/6", "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": "CA229668/MONDO:0009861/006/ci/CA229668/MONDO:0009861/006.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA229668/MONDO:0009861/006/0/1798/1800", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA229668/MONDO:0009861/006/1/1799", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA229668/MONDO:0009861/006/0/1798", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA229668/MONDO:0009861/006", "metadata": { "created": "2024-09-27T22:21:36.048Z", "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 22:21:35 -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": "2eaf4e3c-85c2-49cd-8343-42a8a9e94d1b", "variant": { "@id": "https://reg.genome.network/allele/CA229668", "id": "CAR:CA229668", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000277.1:c.635T>C" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000277.1(PAH):c.635T>C (p.Leu212Pro)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-06-15T11:23:30.161Z" } }, "status": { "code": 200, "name": "OK" } }