{ "data": { "@context": "https://genboree.org/evrepo/api/context", "@id": "https://genboree.org/evrepo/api/summary/classification/0129bef0-6e1d-4f6b-8e4e-2c05721902af/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://genboree.org/evrepo/api/interpretation/CA114372/MONDO:0009861/006/el/0/1828", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA114372/MONDO:0009861/006/ei/1/1829", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "contributionDate": { "date": "2019/4/5", "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://genboree.org/evrepo/api/interpretation/CA114372/MONDO:0009861/006/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA114372/MONDO:0009861/006/ci/EV000000051", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "Two heterologous in vitro expression systems (cell-free rabbit reticulocyte lysates) to assess the residual activities and oligomeric compositions. V245A had PAH enzyme activities 63;39 (% of wt, pcDNA3/IVT).", "contributionDate": { "date": "2019/4/5", "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": "CA114372/MONDO:0009861/006/ci/EV000000051", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/11161839", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA114372/MONDO:0009861/006/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA114372/MONDO:0009861/006/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA114372/MONDO:0009861/006/0/1828", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA114372/MONDO:0009861/006/el/0/1798", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA114372/MONDO:0009861/006/ei/1/1799", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "contributionDate": { "date": "2019/4/5", "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://genboree.org/evrepo/api/interpretation/CA114372/MONDO:0009861/006/el/0/1798/1800", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA114372/MONDO:0009861/006/ci/CA114372/MONDO:0009861/006.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "ExAC MAF: 0.00114", "contributionDate": { "date": "2019/4/5", "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": "CA114372/MONDO:0009861/006/ci/CA114372/MONDO:0009861/006.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA114372/MONDO:0009861/006/0/1798/1800", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA114372/MONDO:0009861/006/1/1799", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA114372/MONDO:0009861/006/0/1798", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA114372/MONDO:0009861/006/el/0/1831", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA114372/MONDO:0009861/006/ei/1/1832", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "contributionDate": { "date": "2019/4/5", "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/0018", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "0018", "label": "PP4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA114372/MONDO:0009861/006/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA114372/MONDO:0009861/006/ci/EV000000008", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "Seven centers in France, Italy, Belgium, Germany, and Denmark participated in this collaborative study. In all patients, hyperphenylalaninemia had been detected by national mass screening programs, and PAH deficiency had been assessed after exclusion of a defect in tetrahydrobiopterin metabolism. V245A was seen in 7 MHP patients from 3 different centers. Patients who have phenylalanine levels <600 mmol/liter on a normal diet were classified as having MHP.", "contributionDate": { "date": "2019/4/5", "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": "CA114372/MONDO:0009861/006/ci/EV000000008", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/9634518", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA114372/MONDO:0009861/006/ci/EV000000052", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "Genomic DNA was isolated from total blood of 34 MHP and eight mild PKU probands from unrelated Polish families. V245A was detected in 2 patients (serum Phe levels 442, 394).", "contributionDate": { "date": "2019/4/5", "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": "CA114372/MONDO:0009861/006/ci/EV000000052", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/9298832", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA114372/MONDO:0009861/006/ci/EV000000020", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "One non-PKU HPA patient (F) carries two novel mutations. One is a T-to-C transition at codon 245 in exon 7, resulting in the replacement of valine by alanine (V245A). Serum Phe level 237 umol/liter.", "contributionDate": { "date": "2019/4/5", "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": "CA114372/MONDO:0009861/006/ci/EV000000020", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/7981714", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA114372/MONDO:0009861/006/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA114372/MONDO:0009861/006/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA114372/MONDO:0009861/006/0/1831", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA114372/MONDO:0009861/006/el/0/1747", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA114372/MONDO:0009861/006/ei/1/1748", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "contributionDate": { "date": "2019/4/5", "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://genboree.org/evrepo/api/interpretation/CA114372/MONDO:0009861/006/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA114372/MONDO:0009861/006/ci/CA114372/MONDO:0009861/006.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "Conflicting predictions of pathogenicity: Tolerated in SIFT, Damaging in Polyphen2, MutationTaster.", "contributionDate": { "date": "2019/4/5", "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": "CA114372/MONDO:0009861/006/ci/CA114372/MONDO:0009861/006.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA114372/MONDO:0009861/006/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA114372/MONDO:0009861/006/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA114372/MONDO:0009861/006/0/1747", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA114372/MONDO:0009861/006/el/0/1669", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA114372/MONDO:0009861/006/ei/1/1670", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "contributionDate": { "date": "2019/4/5", "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/0038", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000220", "id": "SEPIO:0000220", "label": "Pathogenic Very Strong" }, "id": "0038", "label": "PM3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA114372/MONDO:0009861/006/el/0/1669/1671", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA114372/MONDO:0009861/006/ci/EV000000053", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "Patient K Genotype: V245A/IVS-12nt1. Patient L: V245A/R408W. Patient M: V245A/Y414C", "contributionDate": { "date": "2019/4/5", "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": "CA114372/MONDO:0009861/006/ci/EV000000053", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/8088845", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA114372/MONDO:0009861/006/ci/EV000000052", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "V245A seen in 2 patients. Once with R252W (varID 584, P/LP). Once with R408W (VarID 577, Pathogenic)", "contributionDate": { "date": "2019/4/5", "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": "CA114372/MONDO:0009861/006/ci/EV000000052", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/9298832", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA114372/MONDO:0009861/006/ci/EV000000020", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "Patient F: V245A/L194P (VarID 102742, P/LP)", "contributionDate": { "date": "2019/4/5", "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": "CA114372/MONDO:0009861/006/ci/EV000000020", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/7981714", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA114372/MONDO:0009861/006/0/1669/1671", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA114372/MONDO:0009861/006/1/1670", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA114372/MONDO:0009861/006/0/1669", "type": "EvidenceLine" }, { "@id": "https://genboree.org/evrepo/api/interpretation/CA114372/MONDO:0009861/006/el/0/1780", "evidenceItem": [ { "@id": "https://genboree.org/evrepo/api/interpretation/CA114372/MONDO:0009861/006/ei/1/1781", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "contributionDate": { "date": "2019/4/5", "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://genboree.org/evrepo/api/interpretation/CA114372/MONDO:0009861/006/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA114372/MONDO:0009861/006/ci/CA114372/MONDO:0009861/006.002", "contribution": [ { "agent": { "@id": "https://genboree.org/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "V245L Pathogenic", "contributionDate": { "date": "2019/4/5", "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": "CA114372/MONDO:0009861/006/ci/CA114372/MONDO:0009861/006.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA114372/MONDO:0009861/006/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA114372/MONDO:0009861/006/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA114372/MONDO:0009861/006/0/1780", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA114372/MONDO:0009861/006", "metadata": { "created": "2024-09-23T16:43:01.413Z", "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": "Mon, 23 Sep 2024 16:43:01 -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": "0129bef0-6e1d-4f6b-8e4e-2c05721902af", "variant": { "@id": "https://reg.genome.network/allele/CA114372", "id": "CAR:CA114372", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000277.2:c.734T>C" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000277.2(PAH):c.734T>C (p.Val245Ala)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://genboree.org/evrepo/api/summarysrvc", "when": "2026-06-12T03:33:59.405Z" } }, "status": { "code": 200, "name": "OK" } }