{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/d8f603d6-ea02-46e0-aba3-29f60f0b30b6/doc/sepio/version/1.0.0", "assertionMethod": { "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/135637575", "label": "ClinGen PTEN Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for PTEN Version 3.1.0", "type": "VariantPathogenicityInterpretationGuideline", "version": "3.1.0" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0017623", "id": "MONDO:0017623", "label": "PTEN hamartoma tumor syndrome", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA000245/MONDO:0017623/003/el/0/1624", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA000245/MONDO:0017623/003/ei/1/1625", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50012_EP15519033251287", "id": "CG-PCER-AGENT:CG_50012_EP15519033251287", "type": "Agent" }, "contributionDate": { "date": "2026/6/26", "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/CA000245/MONDO:0017623/003/el/0/1624/1626", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA000245/MONDO:0017623/003/ci/CA000245/MONDO:0017623/003.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50012_EP15519033251287", "id": "CG-PCER-AGENT:CG_50012_EP15519033251287", "type": "Agent" }, "comments": "Adult patient presumed de novo with macrocephaly, developmental delay, lipoma, Hashimoto's thyroiditis, arteriovenous malformation, and breast fibroadenomas (Phenotype score +19, does not meet PS4; meets PM6) (PMID 40407579). Pediatric patient presumed de novo with macrocephaly and autism (Phenotype score +4 (including autism), does not meet PS4; meets PM6) (PMID 22595938). Adult patient confirmed de novo (WES trio +sibling) with RC, Hashimoto's Thyroiditis, and thyroid cancer (dx 20-49). (Phenotype score +9, does not meet PS4; meets PS2) (PMID 30233642).", "contributionDate": { "date": "2026/6/26", "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": "CA000245/MONDO:0017623/003/ci/CA000245/MONDO:0017623/003.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA000245/MONDO:0017623/003/0/1624/1626", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA000245/MONDO:0017623/003/1/1625", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA000245/MONDO:0017623/003/0/1624", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA000245/MONDO:0017623/003/el/0/1594", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA000245/MONDO:0017623/003/ei/1/1595", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50012_EP15519033251287", "id": "CG-PCER-AGENT:CG_50012_EP15519033251287", "type": "Agent" }, "contributionDate": { "date": "2026/6/26", "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/CA000245/MONDO:0017623/003/el/0/1594/1596", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA000245/MONDO:0017623/003/ci/CA000245/MONDO:0017623/003.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50012_EP15519033251287", "id": "CG-PCER-AGENT:CG_50012_EP15519033251287", "type": "Agent" }, "comments": "This nonsense mutation causes a truncation 5’ to c.1121 in a biologically-relevant transcript (NM_000314.8).", "contributionDate": { "date": "2026/6/26", "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": "CA000245/MONDO:0017623/003/ci/CA000245/MONDO:0017623/003.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA000245/MONDO:0017623/003/0/1594/1596", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA000245/MONDO:0017623/003/1/1595", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA000245/MONDO:0017623/003/0/1594", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA000245/MONDO:0017623/003/el/0/1678", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA000245/MONDO:0017623/003/ei/1/1679", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50012_EP15519033251287", "id": "CG-PCER-AGENT:CG_50012_EP15519033251287", "type": "Agent" }, "contributionDate": { "date": "2026/6/26", "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/CA000245/MONDO:0017623/003/el/0/1678/1680", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA000245/MONDO:0017623/003/ci/CA000245/MONDO:0017623/003.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50012_EP15519033251287", "id": "CG-PCER-AGENT:CG_50012_EP15519033251287", "type": "Agent" }, "comments": "Co-segregation with disease in multiple affected family members, with 3 family members affected (PMID: 10353779).", "contributionDate": { "date": "2026/6/26", "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": "CA000245/MONDO:0017623/003/ci/CA000245/MONDO:0017623/003.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA000245/MONDO:0017623/003/0/1678/1680", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA000245/MONDO:0017623/003/1/1679", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA000245/MONDO:0017623/003/0/1678", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA000245/MONDO:0017623/003/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA000245/MONDO:0017623/003/ei/1/1637", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50012_EP15519033251287", "id": "CG-PCER-AGENT:CG_50012_EP15519033251287", "type": "Agent" }, "contributionDate": { "date": "2026/6/26", "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/CA000245/MONDO:0017623/003/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA000245/MONDO:0017623/003/ci/CA000245/MONDO:0017623/003.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50012_EP15519033251287", "id": "CG-PCER-AGENT:CG_50012_EP15519033251287", "type": "Agent" }, "comments": "Variant is present at <0.00001 allele frequency and <0.00002 in a subpopulation with multiple alleles in gnomAD (v4).", "contributionDate": { "date": "2026/6/26", "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": "CA000245/MONDO:0017623/003/ci/CA000245/MONDO:0017623/003.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA000245/MONDO:0017623/003/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA000245/MONDO:0017623/003/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA000245/MONDO:0017623/003/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA000245/MONDO:0017623/003/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA000245/MONDO:0017623/003/ei/1/1736", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50012_EP15519033251287", "id": "CG-PCER-AGENT:CG_50012_EP15519033251287", "type": "Agent" }, "contributionDate": { "date": "2026/6/26", "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/CA000245/MONDO:0017623/003/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA000245/MONDO:0017623/003/ci/CA000245/MONDO:0017623/003.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50012_EP15519033251287", "id": "CG-PCER-AGENT:CG_50012_EP15519033251287", "type": "Agent" }, "comments": "Probands with total specificity score of 5. Probands are as follows: Pediatric patient with macrocephaly, developmental delay, and penile freckling. Phenotype score +7, +1 proband point (PMID 10353779). Pediatric patient presumed de novo with macrocephaly, developmental delay, arteriovenous hemangioma, acral keratoses, and a lipoma. Phenotype score +7, +1 proband point (PMID 22595938). Pediatric patient presumed de novo with macrocephaly, developmental delay, and multiple lipomas. Phenotype score +5, +1 proband point (PMID 10232405). Pediatric patient presumed de novo with macrocephaly, hemangiomas, increased perivascular space, and hamartomatous polyps. Phenotype Score +9, +1 proband point (PMID 24052722). Pediatric patient presumed de novo with extreme macrocephaly, developmental delay and autism, thyroid nodules, and a vascular malformation. Phenotype Score +9, +1 proband point (PMID 28526761).", "contributionDate": { "date": "2026/6/26", "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": "CA000245/MONDO:0017623/003/ci/CA000245/MONDO:0017623/003.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA000245/MONDO:0017623/003/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA000245/MONDO:0017623/003/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA000245/MONDO:0017623/003/0/1735", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA000245/MONDO:0017623/003", "metadata": { "created": "2026-06-26T16:19:49.701Z", "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, 26 Jun 2026 16:19:49 -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": "d8f603d6-ea02-46e0-aba3-29f60f0b30b6", "variant": { "@id": "https://reg.genome.network/allele/CA000245", "id": "CAR:CA000245", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000314.8:c.1003C>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000314.8(PTEN):c.1003C>T (p.Arg335Ter)" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-14T00:00:36.949Z" } }, "status": { "code": 200, "name": "OK" } }