{ "data": [ { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/d4782d4a-27b7-4626-acc7-f8758d33384d/doc/sepio/version/1.0.0", "assertionMethod": { "type": "VariantPathogenicityInterpretationGuideline" }, "condition": { "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0019497", "id": "MONDO:0019497", "label": "nonsyndromic genetic deafness", "type": "GeneticCondition" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA253889/MONDO:0019497/005/el/0/1804", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA253889/MONDO:0019497/005/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/CA253889/MONDO:0019497/005/el/0/1804/1806", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA253889/MONDO:0019497/005/ci/CA253889/MONDO:0019497/005.002", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "This variant is present in 1/111716 European alleles. This frequency meets our PM2 threshold for AD hearing loss", "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": "CA253889/MONDO:0019497/005/ci/CA253889/MONDO:0019497/005.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA253889/MONDO:0019497/005/0/1804/1806", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA253889/MONDO:0019497/005/1/1805", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA253889/MONDO:0019497/005/0/1804", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA253889/MONDO:0019497/005/el/0/1768", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA253889/MONDO:0019497/005/ei/1/1769", "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/0071", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000328", "id": "SEPIO:0000328", "label": "Benign Strong" }, "id": "0071", "label": "BS4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA253889/MONDO:0019497/005/el/0/1768/1770", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA253889/MONDO:0019497/005/ci/EV000000398", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "Eight of nine subjects with the same P51S variant in COCH had similar rediologic lesions indicating focal sclerosis of one or more semiciruclar canals. The patients all had hearing loss and vestibular involvement consistent with DFNA9. The authors assert that this is a new phenotype associated with the variant/COCH gene.", "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": "CA253889/MONDO:0019497/005/ci/EV000000398", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/24662630", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA253889/MONDO:0019497/005/ci/EV000000399", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "Large Dutch family with HL and vestibular involvement segregating with variant. 44 affected family members. 30 participated in the study.", "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": "CA253889/MONDO:0019497/005/ci/EV000000399", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/16151338", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA253889/MONDO:0019497/005/ci/EV000000403", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "Dutch family with AD nonsyndromic progressive sensorineural heraing loss and vestibular involvement. This family had a later age of onset than a previous DFNA9 family. Family W98-011 comprises >200 members 22 of which were genetically analyzed. AD inheritance with no evidence of non-penetrance in the pedigree. Identified 12 affected and 4 \"probably affected members of the nuclear family\" who were sequenced. This meets criteria for PP1_Strong.", "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": "CA253889/MONDO:0019497/005/ci/EV000000403", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/9931344", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA253889/MONDO:0019497/005/0/1768/1770", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA253889/MONDO:0019497/005/1/1769", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA253889/MONDO:0019497/005/0/1768", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA253889/MONDO:0019497/005/el/0/1588", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA253889/MONDO:0019497/005/ei/1/1589", "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/0072", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000328", "id": "SEPIO:0000328", "label": "Benign Strong" }, "id": "0072", "label": "BS3", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA253889/MONDO:0019497/005/el/0/1588/1590", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA253889/MONDO:0019497/005/ci/EV000000099", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "The variant was found not to impede secretion in this study dispite previous reports indicating that it may. (Grabski 2003, Robertson 2003, Street 2005, and Yao 2010 are all cited).", "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": "CA253889/MONDO:0019497/005/ci/EV000000099", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/25230692", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA253889/MONDO:0019497/005/ci/EV000000404", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "This study investigated the inner ear tissues from a post Mortem sample obtained from a member of a DFNA9 Dutch family with a segregating p.P51S variant, They compared the bone sampels to WT and -/- COCH mice. They also conducted expression studies. They found that the p.P51S variant had stable expression of COCH and therefore does not cause loss of the protein. There is no evidence directly implicating the variant but it does support the COCH gene's role in disease.", "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": "CA253889/MONDO:0019497/005/ci/EV000000404", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/16481359", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA253889/MONDO:0019497/005/ci/EV000000406", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "This study showed that all the variants localized in the peri-nuclear Gogli region but that the p.P51S variants showed signfiicant staining within the Golgi complex similar to WT cochlin. The p.P51S variant also showed extreacellular deposition that slightly co-localized with fibronectin. They concluded that the extracellular deposits are indistinguishable form WT cochlin and yet since they cause the same histopathoglogy as the other mutants, it is likely that they are unable to interact with the ECM components. This should not be counted towards pathogenicity.", "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": "CA253889/MONDO:0019497/005/ci/EV000000406", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/12928864", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA253889/MONDO:0019497/005/ci/EV000000405", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "This study found that the P51S variant and found that this variant was one of the mutants that showed a varying degreee of increase in the levels of full-length cochlin and decreases in the levels of processed forms", "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": "CA253889/MONDO:0019497/005/ci/EV000000405", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/20228067", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA253889/MONDO:0019497/005/ci/EV000000400", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "Investigated cochlins containing p.P51S as well as p.V66G, p.G88E, p.I109T, p.W117R, plV123E, and p.C162Y variants. Found that all variants demonstrate reduced cleavage by aggrecanase. This suggestes that the impaired post-translational cleavage by aggrecanase may be a mechanism underlying the disease. See figure 3.", "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": "CA253889/MONDO:0019497/005/ci/EV000000400", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/26256111", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA253889/MONDO:0019497/005/0/1588/1590", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA253889/MONDO:0019497/005/1/1589", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA253889/MONDO:0019497/005/0/1588", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA253889/MONDO:0019497/005/el/0/1579", "evidenceItem": [ { "@id": 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"defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000216", "id": "SEPIO:0000216", "label": "Pathogenic Moderate" }, "id": "0010", "label": "PM6", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA253889/MONDO:0019497/005/el/0/1672/1674", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA253889/MONDO:0019497/005/ci/CA253889/MONDO:0019497/005.002", "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" } ], "id": "CA253889/MONDO:0019497/005/ci/CA253889/MONDO:0019497/005.002", "type": "InfFromBkgrndSciKnow" } ], 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"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/CA253889/MONDO:0019497/005/el/0/1828/1830", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA253889/MONDO:0019497/005/ci/EV000000099", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "The variant was found not to impede secretion in this study dispite previous reports indicating that it may. (Grabski 2003, Robertson 2003, Street 2005, and Yao 2010 are all cited).", "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": "CA253889/MONDO:0019497/005/ci/EV000000099", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/25230692", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA253889/MONDO:0019497/005/ci/EV000000404", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "This study investigated the inner ear tissues from a post Mortem sample obtained from a member of a DFNA9 Dutch family with a segregating p.P51S variant, They compared the bone sampels to WT and -/- COCH mice. They also conducted expression studies. They found that the p.P51S variant had stable expression of COCH and therefore does not cause loss of the protein. There is no evidence directly implicating the variant but it does support the COCH gene's role in disease.", "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": "CA253889/MONDO:0019497/005/ci/EV000000404", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/16481359", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA253889/MONDO:0019497/005/ci/EV000000406", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "This study showed that all the variants localized in the peri-nuclear Gogli region but that the p.P51S variants showed signfiicant staining within the Golgi complex similar to WT cochlin. The p.P51S variant also showed extreacellular deposition that slightly co-localized with fibronectin. They concluded that the extracellular deposits are indistinguishable form WT cochlin and yet since they cause the same histopathoglogy as the other mutants, it is likely that they are unable to interact with the ECM components. This should not be counted towards pathogenicity.", "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": "CA253889/MONDO:0019497/005/ci/EV000000406", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/12928864", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA253889/MONDO:0019497/005/ci/EV000000405", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "This study found that the P51S variant and found that this variant was one of the mutants that showed a varying degreee of increase in the levels of full-length cochlin and decreases in the levels of processed forms", "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": "CA253889/MONDO:0019497/005/ci/EV000000405", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/20228067", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA253889/MONDO:0019497/005/ci/EV000000400", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "Investigated cochlins containing p.P51S as well as p.V66G, p.G88E, p.I109T, p.W117R, plV123E, and p.C162Y variants. Found that all variants demonstrate reduced cleavage by aggrecanase. This suggestes that the impaired post-translational cleavage by aggrecanase may be a mechanism underlying the disease. See figure 3.", "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": "CA253889/MONDO:0019497/005/ci/EV000000400", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/26256111", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA253889/MONDO:0019497/005/0/1828/1830", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA253889/MONDO:0019497/005/1/1829", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA253889/MONDO:0019497/005/0/1828", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA253889/MONDO:0019497/005/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA253889/MONDO:0019497/005/ei/1/1736", "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/0053", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0053", "label": "PS4", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA253889/MONDO:0019497/005/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA253889/MONDO:0019497/005/ci/EV000000399", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "Identified a new Dutc family with progressive hearing loss and vestibular impairment. The family was also found to have the p.Pro51Ser variant segregating with disease. They found that hearing started to deteriorate in all mutation carriers around 43 years of age onwards. Vestibular dysfunction started around age 34.", "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": "CA253889/MONDO:0019497/005/ci/EV000000399", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/16151338", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA253889/MONDO:0019497/005/ci/EV000000402", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "This study identified 10 familes with the same haplotype who carried the P51S and had it segregate with disease in their families.The families were all Dutch or Belgian. They concluded that these families must have a common ancestor.", "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": "CA253889/MONDO:0019497/005/ci/EV000000402", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/11332404", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA253889/MONDO:0019497/005/ci/EV000000401", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "Identified an Austrian family with AD segregating progressive late onset hearing loss who had WES identifiy the c.151C>T missense (p.Pro51Ser) variant. The family consists of 4 generations.", "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": "CA253889/MONDO:0019497/005/ci/EV000000401", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/28733840", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA253889/MONDO:0019497/005/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA253889/MONDO:0019497/005/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA253889/MONDO:0019497/005/0/1735", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA253889/MONDO:0019497/005/el/0/1648", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA253889/MONDO:0019497/005/ei/1/1649", "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/0023", "defaultStrength": { "@id": "https://obofoundry.org/sepio/SEPIO:0000330", "id": "SEPIO:0000330", "label": "Pathogenic Strong" }, "id": "0023", "label": "PP1", "type": "Criterion" }, "evidenceLine": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA253889/MONDO:0019497/005/el/0/1648/1650", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA253889/MONDO:0019497/005/ci/EV000000398", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "Eight of nine subjects with the same P51S variant in COCH had similar rediologic lesions indicating focal sclerosis of one or more semiciruclar canals. The patients all had hearing loss and vestibular involvement consistent with DFNA9. The authors assert that this is a new phenotype associated with the variant/COCH gene.", "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": "CA253889/MONDO:0019497/005/ci/EV000000398", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/24662630", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA253889/MONDO:0019497/005/ci/EV000000399", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "Large Dutch family with HL and vestibular involvement segregating with variant. 44 affected family members. 30 participated in the study.", "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": "CA253889/MONDO:0019497/005/ci/EV000000399", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/16151338", "type": "CuratorInference" }, { "@id": "CG-PCER:curatorInference/CA253889/MONDO:0019497/005/ci/EV000000403", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50007_EP155190799758139", "id": "CG-PCER-AGENT:CG_50007_EP155190799758139", "type": "Agent" }, "comments": "Dutch family with AD nonsyndromic progressive sensorineural heraing loss and vestibular involvement. This family had a later age of onset than a previous DFNA9 family. Family W98-011 comprises >200 members 22 of which were genetically analyzed. AD inheritance with no evidence of non-penetrance in the pedigree. Identified 12 affected and 4 \"probably affected members of the nuclear family\" who were sequenced. This meets criteria for PP1_Strong.", "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": "CA253889/MONDO:0019497/005/ci/EV000000403", "traceableAuthorStatement": "https://www.ncbi.nlm.nih.gov/pubmed/9931344", "type": "CuratorInference" } ], "id": "CG-PCER-VARINT:CA253889/MONDO:0019497/005/0/1648/1650", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA253889/MONDO:0019497/005/1/1649", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA253889/MONDO:0019497/005/0/1648", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA253889/MONDO:0019497/005", "metadata": { "created": "2024-09-27T19:39:08.178Z", "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 19:39:07 -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": "d4782d4a-27b7-4626-acc7-f8758d33384d", "variant": { "@id": "https://reg.genome.network/allele/CA253889", "id": "CAR:CA253889", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_004086.2:c.151C>T" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_004086.2(COCH):c.151C>T (p.Pro51Ser)" } ], "type": "CAR" } } ], "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-14T02:35:56.752Z" } }, "status": { "code": 200, "name": "OK" } }