{ "data": [ { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/dc239e28-ecae-44c9-998a-c69771a041f3/doc/sepio/version/1.0.0", "assertionMethod": { "type": "VariantPathogenicityInterpretationGuideline" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0019501", "id": "MONDO:0019501", "label": "Usher syndrome", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA132454/MONDO:0019501/005/el/0/1597", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA132454/MONDO:0019501/005/ei/1/1598", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "contributionDate": { "date": "2019/7/17", "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/0084", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000327", "id": "SEPIO:0000327", "label": "Benign Supporting" }, "id": "0084", "label": "BP2", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA132454/MONDO:0019501/005/el/0/1597/1599", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA132454/MONDO:0019501/005/ci/EV000000395", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "The Arg302His variant was identified in four individuals with Usher syndrome from Holland, Sweden and Belgium. One individual was heterozygous for Arg302His, which was also in cis with Arg212His (classified as pathogenic or likely pathogenic by LMM and Counsyl in ClinVar). Oneindividual was homozygous, for both Arg302His and Arg212His. Two individuals were found to be heterozygous for only Arg302His.", "contributionDate": { "date": "2019/7/17", "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": "CA132454/MONDO:0019501/005/ci/EV000000395", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/8900236", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA132454/MONDO:0019501/005/0/1597/1599", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA132454/MONDO:0019501/005/1/1598", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA132454/MONDO:0019501/005/0/1597", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA132454/MONDO:0019501/005/el/0/1645", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA132454/MONDO:0019501/005/ei/1/1646", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "contributionDate": { "date": "2019/7/17", "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/0085", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000327", "id": "SEPIO:0000327", "label": "Benign Supporting" }, "id": "0085", "label": "BS3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA132454/MONDO:0019501/005/el/0/1645/1647", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA132454/MONDO:0019501/005/ci/EV000000394", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "Actin-translocating activity revealed the similar velocity of R302H mutant to that of the wild-type, consistent with the actin-activated ATPase activity that showed little difference from the wild-type. In all of the functional assays performed in this study, the R302H mutation showed little effect on the motor activity of myosin VIIa. \nSf9 cells were infected with viruses expressing a construct of human MYO7A that harbored previously reported Ush variants. Construct contained the entire motor domain plus two IQ motifs of myosin VIIa. The Arg302His variant showed little effect on motor activity of MYO7A. Studied ATPase activity (similar to WT), rate of ADP release from actin myosin (all other mutants showed dissociation from actin in presence of ADP, actin translocating velocity was similar to WT). Furthermore, Arg302 is not conserved among members of the myosin superfamily, suggesting that Arg302 is not critical for the authentic function of myosin VIIa. Therefore, they concluded that the R302H mutation is not directly responsible for the USH1B phenotype.", "contributionDate": { "date": "2019/7/17", "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": "CA132454/MONDO:0019501/005/ci/EV000000394", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/18700726", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA132454/MONDO:0019501/005/0/1645/1647", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA132454/MONDO:0019501/005/1/1646", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA132454/MONDO:0019501/005/0/1645", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA132454/MONDO:0019501/005/el/0/1804", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA132454/MONDO:0019501/005/ei/1/1805", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "contributionDate": { "date": "2019/7/17", "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/0070", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000328", "id": "SEPIO:0000328", "label": "Benign Strong" }, "id": "0070", "label": "BS1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA132454/MONDO:0019501/005/el/0/1804/1806", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA132454/MONDO:0019501/005/ci/CA132454/MONDO:0019501/005.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "filtering allele frequency calculated from gnomAD = 0.4% (587/126276) of European chromosomes", "contributionDate": { "date": "2019/7/17", "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": "CA132454/MONDO:0019501/005/ci/CA132454/MONDO:0019501/005.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA132454/MONDO:0019501/005/0/1804/1806", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA132454/MONDO:0019501/005/1/1805", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA132454/MONDO:0019501/005/0/1804", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA132454/MONDO:0019501/005/el/0/1579", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA132454/MONDO:0019501/005/ei/1/1580", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "contributionDate": { "date": "2019/7/17", "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/0078", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000327", "id": "SEPIO:0000327", "label": "Benign Supporting" }, "id": "0078", "label": "BP5", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA132454/MONDO:0019501/005/el/0/1579/1581", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA132454/MONDO:0019501/005/ci/EV000000396", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "reported as likely neutral, 1 patient had two likely pathogenic variants in CDH23 (Arg1219X and Arg1746Gln), another patient had 2 likely pathogenic variants (V72V and 496+1G>T) in USH1C", "contributionDate": { "date": "2019/7/17", "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": "CA132454/MONDO:0019501/005/ci/EV000000396", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/25468891", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA132454/MONDO:0019501/005/0/1579/1581", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA132454/MONDO:0019501/005/1/1580", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA132454/MONDO:0019501/005/0/1579", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA132454/MONDO:0019501/005", "metadata": { "created": "2024-09-27T19:38:39.273Z", "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 19:38:39 -0000", "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)", "version": "1.0.0" }, "statementOutcome": { "@id": "https://loinc.org/LA26334-5", "id": "LN:LA26334-5", "label": "Likely Benign" }, "type": "VariantPathogenicityInterpretation", "uuid": "dc239e28-ecae-44c9-998a-c69771a041f3", "variant": { "@id": "https://reg.genome.network/allele/CA132454", "id": "CAR:CA132454", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000260.3:c.905G>A" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000260.3(MYO7A):c.905G>A (p.Arg302His)" } ], "type": "CAR" } } ], "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-14T23:06:16.692Z" } }, "status": { "code": 200, "name": "OK" } }