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"@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://erepo.genome.network/evrepo/api/interpretation/CA273357/MONDO:0009861/006/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA273357/MONDO:0009861/006/ci/EV000000081", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "We analyzed blood samples of 35 patients, R241C was found in a Taiwanese patient.", "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": "CA273357/MONDO:0009861/006/ci/EV000000081", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/8222245", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA273357/MONDO:0009861/006/ci/EV000000082", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "A total of 20 unrelated PKU families Urinary excretion of biopterin (B), neopterin (N), N/B ratio, and dihydropteridine reductase activities in erythrocytes were measured in Japanese patients detected by mass screening, to exclude biopterin deficiency. R241C was seen in 2 Japanese MHP patients (pretreatment Phe level 6.7 and 7.5 mg/dl).", "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": "CA273357/MONDO:0009861/006/ci/EV000000082", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/11142755", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA273357/MONDO:0009861/006/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA273357/MONDO:0009861/006/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA273357/MONDO:0009861/006/0/1831", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA273357/MONDO:0009861/006/el/0/1828", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA273357/MONDO:0009861/006/ei/1/1829", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/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://erepo.genome.network/evrepo/api/interpretation/CA273357/MONDO:0009861/006/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA273357/MONDO:0009861/006/ci/EV000000080", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "We performed the phenylalanine breath test as reliable method to determine the BH4 responsiveness. Phenylalanine breath test quantitatively measures the conversion of L-[1-13C] phenylalanine to 13CO2 and is a noninvasive and rapid test. A mild HPA case was homozygote of R241C. The phenylalanine breath test exhibited continuous levels of CRR (cumulative recovery rate) of 2.74% (mild HPA/R241C homozygote), as compared to control subjects (15.4%).", "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": "CA273357/MONDO:0009861/006/ci/EV000000080", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/15319459", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA273357/MONDO:0009861/006/ci/EV000000079", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "For identification of whether the R241C mutation causes PKU, expression analysis was performed in mammalian cells. In dot blot\nhybridization of serially diluted RNA of transfected cells, the normal and mutant PAH cCDNA constructs expressed similar\nlevels of mRNA. The PAH activity of the mutant protein was 25 ± 3% (SD) of normal PAH. The mother and the patient had the R241C mutation as heterozygotes.", "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": "CA273357/MONDO:0009861/006/ci/EV000000079", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/7915167", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA273357/MONDO:0009861/006/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA273357/MONDO:0009861/006/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA273357/MONDO:0009861/006/0/1828", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA273357/MONDO:0009861/006/el/0/1651", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA273357/MONDO:0009861/006/ei/1/1652", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/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/0058", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0058", "label": "PM3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA273357/MONDO:0009861/006/el/0/1651/1653", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA273357/MONDO:0009861/006/ci/EV000000082", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50015_EP155190578201949", "id": "CG-PCER-AGENT:CG_50015_EP155190578201949", "type": "Agent" }, "comments": "R241C seen in 2 Japanese MHP patients in trans with R413P (VarID 592, Pathogenic in ClinVar) and R243Q (VarID 591, Pathogenic in ClinVar).", "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": "CA273357/MONDO:0009861/006/ci/EV000000082", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/11142755", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA273357/MONDO:0009861/006/0/1651/1653", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA273357/MONDO:0009861/006/1/1652", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA273357/MONDO:0009861/006/0/1651", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA273357/MONDO:0009861/006", "metadata": { "created": "2024-09-27T19:41:15.402Z", "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 19:41:15 -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": "dd8fcc3c-dde1-42d4-a0f2-31bbafa786a5", "variant": { "@id": "https://reg.genome.network/allele/CA273357", "id": "CAR:CA273357", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000277.1:c.721C>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000277.1(PAH):c.721C>T (p.Arg241Cys)" } ], "type": "CAR" } } ], "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-11-03T06:35:07.253Z" } }, "status": { "code": 200, "name": "OK" } }