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{
"count": 188082,
"next": "https://panelapp.genomicsengland.co.uk/api/v1/activities/?page=2",
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"results": [
{
"created": "2022-08-15T14:55:04.344141Z",
"panel_name": "Haematological malignancies cancer susceptibility",
"panel_id": 59,
"panel_version": "2.34",
"user_name": "Dmitrijs Rots",
"item_type": "entity",
"text": "gene: RAD21 was added\ngene: RAD21 was added to Haematological malignancies cancer susceptibility. Sources: Literature\nMode of inheritance for gene: RAD21 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: RAD21 were set to 35563565\nPhenotypes for gene: RAD21 were set to Children to Lymphoblastic Leukemia or Lymphoma\nPenetrance for gene: RAD21 were set to Incomplete\nMode of pathogenicity for gene: RAD21 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments\nReview for gene: RAD21 was set to GREEN\nAdded comment: >3 cases reported with recurrent RAD21 missense variant with lymphocytic malignancy (ALL or LBL) without CdLS features + functional evidence in 35563565. Sufficient for green rating. \nSources: Literature",
"entity_name": "RAD21",
"entity_type": "gene"
},
{
"created": "2022-08-14T21:18:02.694991Z",
"panel_name": "Dilated cardiomyopathy - adult and teen",
"panel_id": 652,
"panel_version": "1.28",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "Tag Q3_22_NHS_review was removed from gene: RRAGD.",
"entity_name": "RRAGD",
"entity_type": "gene"
},
{
"created": "2022-08-14T21:17:48.551305Z",
"panel_name": "Cardiomyopathies - including childhood onset",
"panel_id": 749,
"panel_version": "1.77",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "Tag Q3_22_NHS_review was removed from gene: RRAGD.",
"entity_name": "RRAGD",
"entity_type": "gene"
},
{
"created": "2022-08-14T21:14:01.844860Z",
"panel_name": "Cardiomyopathies - including childhood onset",
"panel_id": 749,
"panel_version": "1.77",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "commented on gene: RRAGD: Copied this gene from the Renal tubulopathies panel. In 6 cases reported in PMID: 34607910 (Schlingmann et al 2021) the probands also had dilated cardiomyopathy. The 6 patients with Dilated cardiomyopathy were diagnosed with the condition at ages between 6 months and 14 years old.",
"entity_name": "RRAGD",
"entity_type": "gene"
},
{
"created": "2022-08-14T21:12:39.121797Z",
"panel_name": "Cardiomyopathies - including childhood onset",
"panel_id": 749,
"panel_version": "1.77",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "Entity copied from Renal tubulopathies v2.62",
"entity_name": "RRAGD",
"entity_type": "gene"
},
{
"created": "2022-08-14T21:12:39.063710Z",
"panel_name": "Cardiomyopathies - including childhood onset",
"panel_id": 749,
"panel_version": "1.77",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "gene: RRAGD was added\ngene: RRAGD was added to Cardiomyopathies - including childhood onset. Sources: Literature,Expert Review Amber\nQ3_22_rating, Q3_22_NHS_review tags were added to gene: RRAGD.\nMode of inheritance for gene: RRAGD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: RRAGD were set to 34607910\nPhenotypes for gene: RRAGD were set to hypomagnesaemia; cardiomyopathy; tubular renal disease-cardiomyopathy syndrome, MONDO:0019130\nPenetrance for gene: RRAGD were set to Complete\nMode of pathogenicity for gene: RRAGD was set to Other",
"entity_name": "RRAGD",
"entity_type": "gene"
},
{
"created": "2022-08-14T21:11:25.938030Z",
"panel_name": "Dilated cardiomyopathy - adult and teen",
"panel_id": 652,
"panel_version": "1.28",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "Deleted their comment",
"entity_name": "RRAGD",
"entity_type": "gene"
},
{
"created": "2022-08-14T21:11:20.764215Z",
"panel_name": "Dilated cardiomyopathy - adult and teen",
"panel_id": 652,
"panel_version": "1.28",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "changed review comment from: Not associated with a phenotype in OMIM or Gene2Phenotype. \r\n\r\nAs reviewer states PMID: 34607910 (Schlingmann et al 2021) reports 8 cases where patients with hypomagnesaemia were found to have heterozygous (mostly de novo) missense variants in RRAGD. 6 patients also had dilated cardiomyopathy. In addition they report a family with a heterozygous variant in RRAGD that segregated with a kidney phenotype in eight members. Abstract only accessed.; to: Not associated with a phenotype in OMIM or Gene2Phenotype. \r\n\r\nAs reviewer states PMID: 34607910 (Schlingmann et al 2021) reports 8 cases where patients with hypomagnesaemia were found to have heterozygous (mostly de novo) missense variants in RRAGD. 6 patients also had dilated cardiomyopathy. In addition they report a family with a heterozygous variant in RRAGD that segregated with a kidney phenotype in eight members. ",
"entity_name": "RRAGD",
"entity_type": "gene"
},
{
"created": "2022-08-14T21:11:11.393943Z",
"panel_name": "Dilated cardiomyopathy - adult and teen",
"panel_id": 652,
"panel_version": "1.28",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "changed review comment from: Copied this gene from the Renal tubulopathies panel. In 6 cases reported in PMID: 34607910 (Schlingmann et al 2021) the probands also had dilated cardiomyopathy. Abstract only accessed.; to: Copied this gene from the Renal tubulopathies panel. In 6 cases reported in PMID: 34607910 (Schlingmann et al 2021) the probands also had dilated cardiomyopathy. The 6 patients with Dilated cardiomyopathy were diagnosed with the condition at ages between 6 months and 14 years old.",
"entity_name": "RRAGD",
"entity_type": "gene"
},
{
"created": "2022-08-14T21:10:37.529153Z",
"panel_name": "Renal tubulopathies",
"panel_id": 292,
"panel_version": "2.62",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "changed review comment from: Not associated with a phenotype in OMIM or Gene2Phenotype. \r\n\r\nAs reviewer states PMID: 34607910 (Schlingmann et al 2021) reports 8 cases where patients with hypomagnesaemia were found to have heterozygous (mostly de novo) missense variants in RRAGD. 6 patients also had dilated cardiomyopathy. In addition they report a family with a heterozygous variant in RRAGD that segregated with a kidney phenotype in eight members. Abstract only accessed.; to: Not associated with a phenotype in OMIM or Gene2Phenotype. \r\n\r\nAs reviewer states PMID: 34607910 (Schlingmann et al 2021) reports 8 cases where patients with hypomagnesaemia were found to have heterozygous (mostly de novo) missense variants in RRAGD. 6 patients also had dilated cardiomyopathy. In addition they report a family with a heterozygous variant in RRAGD that segregated with a kidney phenotype in eight members. The age of onset was 6 months to 24 years.",
"entity_name": "RRAGD",
"entity_type": "gene"
},
{
"created": "2022-08-14T21:08:34.853932Z",
"panel_name": "Dilated cardiomyopathy - adult and teen",
"panel_id": 652,
"panel_version": "1.28",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "commented on gene: RRAGD: Update on PMID: 34607910 (Schlingmann et al 2021) - the 6 patients with Dilated cardiomyopathy were diagnosed with the condition at ages between 6 months and 14 years old.",
"entity_name": "RRAGD",
"entity_type": "gene"
},
{
"created": "2022-08-14T20:50:09.102476Z",
"panel_name": "DDG2P",
"panel_id": 484,
"panel_version": "2.78",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "commented on gene: TERC",
"entity_name": "TERC",
"entity_type": "gene"
},
{
"created": "2022-08-14T20:45:03.547925Z",
"panel_name": "DDG2P",
"panel_id": 484,
"panel_version": "2.78",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "commented on gene: RMRP",
"entity_name": "RMRP",
"entity_type": "gene"
},
{
"created": "2022-08-14T20:41:26.272365Z",
"panel_name": "DDG2P",
"panel_id": 484,
"panel_version": "2.78",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "commented on gene: COL6A1",
"entity_name": "COL6A1",
"entity_type": "gene"
},
{
"created": "2022-08-14T20:11:40.236197Z",
"panel_name": "Intellectual disability",
"panel_id": 285,
"panel_version": "3.1677",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "Added comment: Comment on mode of inheritance: 3 more cases of monoallelic variants in patients with an intellectual disability phenotype now reported so the mode of inheritance should be changed to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'",
"entity_name": "EMC1",
"entity_type": "gene"
},
{
"created": "2022-08-14T20:11:40.223393Z",
"panel_name": "Intellectual disability",
"panel_id": 285,
"panel_version": "3.1677",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "Mode of inheritance for gene: EMC1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "EMC1",
"entity_type": "gene"
},
{
"created": "2022-08-14T20:10:29.173101Z",
"panel_name": "Intellectual disability",
"panel_id": 285,
"panel_version": "3.1676",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "Tag Q3_22_MOI tag was added to gene: EMC1.",
"entity_name": "EMC1",
"entity_type": "gene"
},
{
"created": "2022-08-14T20:10:05.227316Z",
"panel_name": "Intellectual disability",
"panel_id": 285,
"panel_version": "3.1676",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "commented on gene: EMC1",
"entity_name": "EMC1",
"entity_type": "gene"
},
{
"created": "2022-08-14T18:29:06.947366Z",
"panel_name": "DDG2P",
"panel_id": 484,
"panel_version": "2.78",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "commented on gene: EMC1",
"entity_name": "EMC1",
"entity_type": "gene"
},
{
"created": "2022-08-14T17:40:58.157868Z",
"panel_name": "Genetic epilepsy syndromes",
"panel_id": 402,
"panel_version": "2.572",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "Publications for gene: CNKSR2 were set to 28098945; 25223753; 22511892; 25644381; 28098945; 34266427",
"entity_name": "CNKSR2",
"entity_type": "gene"
},
{
"created": "2022-08-14T17:40:33.311685Z",
"panel_name": "Genetic epilepsy syndromes",
"panel_id": 402,
"panel_version": "2.571",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "commented on gene: CNKSR2",
"entity_name": "CNKSR2",
"entity_type": "gene"
},
{
"created": "2022-08-14T17:39:45.424033Z",
"panel_name": "Intellectual disability",
"panel_id": 285,
"panel_version": "3.1676",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "commented on gene: CNKSR2",
"entity_name": "CNKSR2",
"entity_type": "gene"
},
{
"created": "2022-08-14T16:18:32.150838Z",
"panel_name": "Genetic epilepsy syndromes",
"panel_id": 402,
"panel_version": "2.571",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "changed review comment from: Not associated with a phenotype in OMIM. Has a strong/probable association with 'Epilepsy and intellectual disability' in Gene2Phenotype. \r\n\r\nPMID: 29100083 - Hamdan et al 2017 - performed WGS on 197 individuals with unexplained Developmental and epileptic encephalopathy and pharmaco-resistant seizures and in their unaffected parents. 2 patients reported with heterozygous missense variants in RAB11A, one of which had seizures (c.244C>T [p.Arg82Cys] variant) in addition to developing severe ID. 2 other individuals with missense variants in RAB11A and some phenotypic data from the DDD project are described but neither had seizures.\r\n\r\nPMID: 33875846 - Bertoli-Avella et al 2021 - in a large study of patients with no initial diagnostic variants identified by ES/GS, they identified two different heterozygous missense variants in RAB11A in two unrelated patients (NM_004663.4: c.375G>T, p. Lys125Asn and NM_004663.4: c.380A>G, p. Asp127Gly). Little patient information but the patient with the p. Asp127Gly variant is reported to have refractory epileptic spasms. Both had brain anomalies and intellectual disability reported. ; to: Not associated with a phenotype in OMIM. Has a strong/probable association with 'Epilepsy and intellectual disability' in Gene2Phenotype. \r\n\r\nPMID: 29100083 - Hamdan et al 2017 - performed WGS on 197 individuals with unexplained Developmental and epileptic encephalopathy and pharmaco-resistant seizures and their unaffected parents. 2 patients reported with heterozygous missense variants in RAB11A, one of which had seizures (c.244C>T [p.Arg82Cys] variant) in addition to developing severe ID. 2 other individuals with missense variants in RAB11A and some phenotypic data from the DDD project are described but neither had seizures.\r\n\r\nPMID: 33875846 - Bertoli-Avella et al 2021 - in a large study of patients with no initial diagnostic variants identified by ES/GS, they identified two different heterozygous missense variants in RAB11A in two unrelated patients (NM_004663.4: c.375G>T, p. Lys125Asn and NM_004663.4: c.380A>G, p. Asp127Gly). Little patient information but the patient with the p. Asp127Gly variant is reported to have refractory epileptic spasms. Both had brain anomalies and intellectual disability reported. ",
"entity_name": "RAB11A",
"entity_type": "gene"
},
{
"created": "2022-08-14T13:19:26.206945Z",
"panel_name": "Fetal anomalies",
"panel_id": 478,
"panel_version": "1.904",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "Classified gene: RAB11A as Amber List (moderate evidence)",
"entity_name": "RAB11A",
"entity_type": "gene"
},
{
"created": "2022-08-14T13:19:26.203963Z",
"panel_name": "Fetal anomalies",
"panel_id": 478,
"panel_version": "1.904",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "Added comment: Comment on list classification: Leaving the rating as amber for now, but with a recommendation of GREEN rating following GMS expert review as to whether the brain anomaly/microcephaly phenotype observed in 5 individuals with missense variants in RAB11A is appropriate for this panel.",
"entity_name": "RAB11A",
"entity_type": "gene"
},
{
"created": "2022-08-14T13:19:26.187970Z",
"panel_name": "Fetal anomalies",
"panel_id": 478,
"panel_version": "1.904",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "Gene: rab11a has been classified as Amber List (Moderate Evidence).",
"entity_name": "RAB11A",
"entity_type": "gene"
},
{
"created": "2022-08-14T13:17:43.055647Z",
"panel_name": "Fetal anomalies",
"panel_id": 478,
"panel_version": "1.903",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "Phenotypes for gene: RAB11A were changed from Epilepsy and intellectual disability to microcephaly, HP:0000252; brain anomalies; Intellectual disability, HP:0001249",
"entity_name": "RAB11A",
"entity_type": "gene"
},
{
"created": "2022-08-14T13:15:44.920292Z",
"panel_name": "Fetal anomalies",
"panel_id": 478,
"panel_version": "1.902",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "Added comment: Comment on mode of pathogenicity: All missense variants but no functional data available.",
"entity_name": "RAB11A",
"entity_type": "gene"
},
{
"created": "2022-08-14T13:15:44.899583Z",
"panel_name": "Fetal anomalies",
"panel_id": 478,
"panel_version": "1.902",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "Mode of pathogenicity for gene: RAB11A was changed from to Other",
"entity_name": "RAB11A",
"entity_type": "gene"
},
{
"created": "2022-08-14T13:15:09.379416Z",
"panel_name": "Fetal anomalies",
"panel_id": 478,
"panel_version": "1.901",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "Publications for gene: RAB11A were set to ",
"entity_name": "RAB11A",
"entity_type": "gene"
},
{
"created": "2022-08-14T13:14:43.912754Z",
"panel_name": "Fetal anomalies",
"panel_id": 478,
"panel_version": "1.900",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "Tag Q3_22_rating tag was added to gene: RAB11A.\nTag Q3_22_expert_review tag was added to gene: RAB11A.",
"entity_name": "RAB11A",
"entity_type": "gene"
},
{
"created": "2022-08-14T13:14:15.700884Z",
"panel_name": "Fetal anomalies",
"panel_id": 478,
"panel_version": "1.900",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "changed review comment from: PMID: 29100083 - Hamdan et al 2017 - performed WGS on 197 individuals with unexplained Developmental and epileptic encephalopathy and pharmaco-resistant seizures and in their unaffected parents. 2 patients reported with heterozygous missense variants in RAB11A, one of which had seizures (c.244C>T [p.Arg82Cys] variant)\r\nin addition to developing severe ID. 2 other individuals with missense variants in RAB11A and some phenotypic data from the DDD project are described. For 3 of the 4 individuals there are brain MRI data which indicate brain abnormalities including partial agenesis of the corpus callosum, or thin corpus collosum. \r\n\r\nPMID: 33875846 - Bertoli-Avella et al 2021 - in a large study of patients with no initial diagnostic variants identified by ES/GS, they identified two different heterozygous missense variants in RAB11A in two unrelated patients (NM_004663.4: c.375G>T, p. Lys125Asn and NM_004663.4: c.380A>G, p. Asp127Gly). Both are reported to have microcephaly (degree not stated) and brain anomalies (both with agenesis of corpus callosum, and one with additional abnormal cortical gyration, mylation abnormalites).; to: PMID: 29100083 - Hamdan et al 2017 - performed WGS on 197 individuals with unexplained Developmental and epileptic encephalopathy and pharmaco-resistant seizures and in their unaffected parents. 2 patients reported with heterozygous missense variants in RAB11A, one of which had seizures (c.244C>T [p.Arg82Cys] variant)\r\nin addition to developing severe ID. 2 other individuals with missense variants in RAB11A and some phenotypic data from the DDD project are described. For 3 of the 4 individuals there are brain MRI data which indicate brain abnormalities including partial agenesis of the corpus callosum, or thin corpus collosum. \r\n\r\nPMID: 33875846 - Bertoli-Avella et al 2021 - in a large study of patients with no initial diagnostic variants identified by ES/GS, they identified two different heterozygous missense variants in RAB11A in two unrelated patients (NM_004663.4: c.375G>T, p. Lys125Asn and NM_004663.4: c.380A>G, p. Asp127Gly). Both are reported to have microcephaly (degree not stated) and brain anomalies (both with agenesis of corpus callosum, and one with additional abnormal cortical gyration, myelination abnormalites).",
"entity_name": "RAB11A",
"entity_type": "gene"
},
{
"created": "2022-08-14T13:13:00.719270Z",
"panel_name": "Fetal anomalies",
"panel_id": 478,
"panel_version": "1.900",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "commented on gene: RAB11A",
"entity_name": "RAB11A",
"entity_type": "gene"
},
{
"created": "2022-08-14T12:54:29.914357Z",
"panel_name": "Genetic epilepsy syndromes",
"panel_id": 402,
"panel_version": "2.571",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "changed review comment from: Not associated with a phenotype in OMIM. Has a strong/probable association with 'Epilepsy and intellectual disability' in Gene2Phenotype. \r\n\r\nPMID: 29100083 - Hamdan et al 2017 - performed WGS on 197 individuals with unexplained Developmental and epileptic encephalopathy and pharmaco-resistant seizures and in their unaffected parents. 2 patients reported with heterozygous missense variants in RAB11A, one of which had seizures (c.244C>T [p.Arg82Cys] variant)\r\n in addition to developing severe ID. \r\n\r\nPMID: 33875846 - Bertoli-Avella et al 2021 - in a large study of patients with no initial diagnostic variants identified by ES/GS, they identified two different heterozygous missense variants in RAB11A in two unrelated patients (NM_004663.4: c.375G>T, p. Lys125Asn and NM_004663.4: c.380A>G, p. Asp127Gly). Little patient information but the patient with the p. Asp127Gly variant is reported to have refractory epileptic spasms. Both had brain anomalies and intellectual disability reported. 2 other individuals with missense variants in RAB11A and some phenotypic data from the DDD project are described but neither had seizures.; to: Not associated with a phenotype in OMIM. Has a strong/probable association with 'Epilepsy and intellectual disability' in Gene2Phenotype. \r\n\r\nPMID: 29100083 - Hamdan et al 2017 - performed WGS on 197 individuals with unexplained Developmental and epileptic encephalopathy and pharmaco-resistant seizures and in their unaffected parents. 2 patients reported with heterozygous missense variants in RAB11A, one of which had seizures (c.244C>T [p.Arg82Cys] variant) in addition to developing severe ID. 2 other individuals with missense variants in RAB11A and some phenotypic data from the DDD project are described but neither had seizures.\r\n\r\nPMID: 33875846 - Bertoli-Avella et al 2021 - in a large study of patients with no initial diagnostic variants identified by ES/GS, they identified two different heterozygous missense variants in RAB11A in two unrelated patients (NM_004663.4: c.375G>T, p. Lys125Asn and NM_004663.4: c.380A>G, p. Asp127Gly). Little patient information but the patient with the p. Asp127Gly variant is reported to have refractory epileptic spasms. Both had brain anomalies and intellectual disability reported. ",
"entity_name": "RAB11A",
"entity_type": "gene"
},
{
"created": "2022-08-13T15:35:17.914696Z",
"panel_name": "Genetic epilepsy syndromes",
"panel_id": 402,
"panel_version": "2.571",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "Classified gene: RAB11A as Amber List (moderate evidence)",
"entity_name": "RAB11A",
"entity_type": "gene"
},
{
"created": "2022-08-13T15:35:17.910528Z",
"panel_name": "Genetic epilepsy syndromes",
"panel_id": 402,
"panel_version": "2.571",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "Added comment: Comment on list classification: Promoting from red to amber. 2 patients reported with seizures, 1 each in PMID: 29100083 and PMID: 33875846 but little clinical information.",
"entity_name": "RAB11A",
"entity_type": "gene"
},
{
"created": "2022-08-13T15:35:17.883901Z",
"panel_name": "Genetic epilepsy syndromes",
"panel_id": 402,
"panel_version": "2.571",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "Gene: rab11a has been classified as Amber List (Moderate Evidence).",
"entity_name": "RAB11A",
"entity_type": "gene"
},
{
"created": "2022-08-13T15:33:55.101982Z",
"panel_name": "Genetic epilepsy syndromes",
"panel_id": 402,
"panel_version": "2.570",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "commented on gene: RAB11A",
"entity_name": "RAB11A",
"entity_type": "gene"
},
{
"created": "2022-08-13T15:18:26.846850Z",
"panel_name": "Intellectual disability",
"panel_id": 285,
"panel_version": "3.1676",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "changed review comment from: PMID: 33875846 - Bertoli-Avella et al 2021 - in a large study of patients with no initial diagnostic variants identified by ES/GS they identified two different heterozygous missense variants in RAB11A in two unrelated patients (NM_004663.4: c.375G>T, p. Lys125Asn and NM_004663.4: c.380A>G, p. Asp127Gly). One was de-novo. Little patient information but both had brain anomalies and intellectual disability reported. 1 had seizures.; to: PMID: 33875846 - Bertoli-Avella et al 2021 - in a large study of patients with no initial diagnostic variants identified by ES/GS, they identified two different heterozygous missense variants in RAB11A in two unrelated patients (NM_004663.4: c.375G>T, p. Lys125Asn and NM_004663.4: c.380A>G, p. Asp127Gly). One was de-novo. Little patient information but both had brain anomalies and intellectual disability reported. 1 had seizures.",
"entity_name": "RAB11A",
"entity_type": "gene"
},
{
"created": "2022-08-11T17:44:52.155862Z",
"panel_name": "Intellectual disability",
"panel_id": 285,
"panel_version": "3.1676",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "changed review comment from: PMID: 33875846 - Bertoli-Avella et al 2021 - in a large study of patients with no initial diagnostic variants identified by ES/GS they identified two different heterozygous missense variants in RAB11A in two unrelated patients. One was de-novo. Little patient information but both had brain anomalies and intellectual disability reported. 1 had seizures.; to: PMID: 33875846 - Bertoli-Avella et al 2021 - in a large study of patients with no initial diagnostic variants identified by ES/GS they identified two different heterozygous missense variants in RAB11A in two unrelated patients (NM_004663.4: c.375G>T, p. Lys125Asn and NM_004663.4: c.380A>G, p. Asp127Gly). One was de-novo. Little patient information but both had brain anomalies and intellectual disability reported. 1 had seizures.",
"entity_name": "RAB11A",
"entity_type": "gene"
},
{
"created": "2022-08-11T17:36:43.417513Z",
"panel_name": "Genetic epilepsy syndromes",
"panel_id": 402,
"panel_version": "2.570",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "gene: RAB11A was added\ngene: RAB11A was added to Genetic epilepsy syndromes. Sources: Literature\nMode of inheritance for gene: RAB11A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: RAB11A were set to 29100083; 33875846\nPhenotypes for gene: RAB11A were set to Global developmental delay, HP:0001263; Intellectual disability, HP:0001249; seizures",
"entity_name": "RAB11A",
"entity_type": "gene"
},
{
"created": "2022-08-11T17:32:31.781526Z",
"panel_name": "Intellectual disability",
"panel_id": 285,
"panel_version": "3.1676",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "Classified gene: RAB11A as Amber List (moderate evidence)",
"entity_name": "RAB11A",
"entity_type": "gene"
},
{
"created": "2022-08-11T17:32:31.772188Z",
"panel_name": "Intellectual disability",
"panel_id": 285,
"panel_version": "3.1676",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "Added comment: Comment on list classification: Leaving the rating as amber just now, but with a recommendation of GREEN rating following GMS review. There are now 6 unrelated individuals with an intellectual disability phenotype reported and missense variants in this gene. Although there is little clinical data available the number of cases adds weight to this gene-disease association.",
"entity_name": "RAB11A",
"entity_type": "gene"
},
{
"created": "2022-08-11T17:32:31.739554Z",
"panel_name": "Intellectual disability",
"panel_id": 285,
"panel_version": "3.1676",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "Gene: rab11a has been classified as Amber List (Moderate Evidence).",
"entity_name": "RAB11A",
"entity_type": "gene"
},
{
"created": "2022-08-11T17:29:33.121296Z",
"panel_name": "Intellectual disability",
"panel_id": 285,
"panel_version": "3.1675",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "Phenotypes for gene: RAB11A were changed from Global developmental delay; Global developmental delay, Intellectual disability; Intellectual disability to Global developmental delay, HP:0001263; Intellectual disability, HP:0001249",
"entity_name": "RAB11A",
"entity_type": "gene"
},
{
"created": "2022-08-11T17:25:55.614450Z",
"panel_name": "Intellectual disability",
"panel_id": 285,
"panel_version": "3.1674",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "Publications for gene: RAB11A were set to 29100083",
"entity_name": "RAB11A",
"entity_type": "gene"
},
{
"created": "2022-08-11T17:25:21.106758Z",
"panel_name": "Intellectual disability",
"panel_id": 285,
"panel_version": "3.1673",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "Tag Q3_22_rating tag was added to gene: RAB11A.",
"entity_name": "RAB11A",
"entity_type": "gene"
},
{
"created": "2022-08-11T17:25:02.635199Z",
"panel_name": "Intellectual disability",
"panel_id": 285,
"panel_version": "3.1673",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "commented on gene: RAB11A",
"entity_name": "RAB11A",
"entity_type": "gene"
},
{
"created": "2022-08-11T17:16:26.205912Z",
"panel_name": "Genomic imprinting",
"panel_id": 227,
"panel_version": "0.138",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "commented on gene: MYH6: There is no evidence that this gene is imprinted. The assignment of the mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) when this gene was added to PanelApp (28 Nov 2016)(https://panelapp.genomicsengland.co.uk/panels/212/gene/MYH6/#!) was an error.",
"entity_name": "MYH6",
"entity_type": "gene"
},
{
"created": "2022-08-11T17:08:20.296084Z",
"panel_name": "DDG2P",
"panel_id": 484,
"panel_version": "2.78",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "commented on gene: RAB11A",
"entity_name": "RAB11A",
"entity_type": "gene"
},
{
"created": "2022-08-11T15:47:41.870435Z",
"panel_name": "Intellectual disability",
"panel_id": 285,
"panel_version": "3.1673",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "edited their review of gene: FBXW7: Changed rating: GREEN",
"entity_name": "FBXW7",
"entity_type": "gene"
},
{
"created": "2022-08-11T15:47:16.144747Z",
"panel_name": "Intellectual disability",
"panel_id": 285,
"panel_version": "3.1673",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "Classified gene: FBXW7 as Amber List (moderate evidence)",
"entity_name": "FBXW7",
"entity_type": "gene"
},
{
"created": "2022-08-11T15:47:16.141247Z",
"panel_name": "Intellectual disability",
"panel_id": 285,
"panel_version": "3.1673",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.",
"entity_name": "FBXW7",
"entity_type": "gene"
},
{
"created": "2022-08-11T15:47:16.119576Z",
"panel_name": "Intellectual disability",
"panel_id": 285,
"panel_version": "3.1673",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "Gene: fbxw7 has been classified as Amber List (Moderate Evidence).",
"entity_name": "FBXW7",
"entity_type": "gene"
},
{
"created": "2022-08-11T15:46:15.711574Z",
"panel_name": "Intellectual disability",
"panel_id": 285,
"panel_version": "3.1672",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "Tag Q3_22_rating tag was added to gene: FBXW7.\nTag Q3_22_MOI tag was added to gene: FBXW7.\nTag Q3_22_phenotype tag was added to gene: FBXW7.",
"entity_name": "FBXW7",
"entity_type": "gene"
},
{
"created": "2022-08-11T15:36:13.257255Z",
"panel_name": "Intellectual disability",
"panel_id": 285,
"panel_version": "3.1672",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "commented on gene: FBXW7",
"entity_name": "FBXW7",
"entity_type": "gene"
},
{
"created": "2022-08-11T14:42:05.279309Z",
"panel_name": "Fetal anomalies",
"panel_id": 478,
"panel_version": "1.900",
"user_name": "Rhiannon Mellis",
"item_type": "entity",
"text": "reviewed gene: EDA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None",
"entity_name": "EDA",
"entity_type": "gene"
},
{
"created": "2022-08-11T14:29:05.980036Z",
"panel_name": "Fetal anomalies",
"panel_id": 478,
"panel_version": "1.900",
"user_name": "Rhiannon Mellis",
"item_type": "entity",
"text": "gene: CHRM3 was added\ngene: CHRM3 was added to Fetal anomalies. Sources: Expert Review,Literature\nMode of inheritance for gene: CHRM3 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: CHRM3 were set to PMID: 22077972; 31441039; 10944224\nPhenotypes for gene: CHRM3 were set to Prune belly syndrome; Megacystis\nReview for gene: CHRM3 was set to AMBER\nAdded comment: This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs.\r\n\r\nClinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH).\r\n\r\nOutcome of review: May be fetally relevant but currently limited evidence, support adding to the Fetal anomalies panel as Amber gene.\r\n\r\nDetails of review:\r\nDiscussed as a potential cause of megacystis. Currently Red on Panelapp CAKUT panel (2016) because at that time there was only 1 reported family and a mouse model. The unpublished data mentioned in that panelapp review (from Adrian Woolf, Manchester) is now published so now 2 families PMID: 22077972; 31441039 plus a mouse model PMID: 10944224. However, prenatal findings (distended bladder and unilateral hydronephrosis) only documented for one individual. More evidence of prenatal phenotype would be helpful. \nSources: Expert Review, Literature",
"entity_name": "CHRM3",
"entity_type": "gene"
},
{
"created": "2022-08-11T14:16:22.904348Z",
"panel_name": "Fetal anomalies",
"panel_id": 478,
"panel_version": "1.900",
"user_name": "Rhiannon Mellis",
"item_type": "entity",
"text": "commented on gene: DEPDC5: This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs.\r\n\r\nClinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH).\r\n\r\nOutcome of review: May be fetally relevant but currently limited evidence, support adding to the Fetal anomalies panel as Amber gene.\r\n\r\nCurrently rated Green on the following other PanelApp panel(s): Intellectual disability, Genetics epilepsies. Amber on cortical malformations panel.\r\n\r\nDetails of review:\r\nPreviously reviewed as Red because only associated with familial epilepsy without structural brain anomalies (AD - caused by het LOF variants) but data presented by Dr Lara Menzies at CGS Spring Meeting 2021 suggests that there may also be a biallelic phenotype with hypomorphic variants. 5 cases presented from 3 unrelated Irish traveller families with significant polymicrogyria and macrocephaly as well as seizures and severe dev delay. At least 2 of the cases had prenatal features: ventriculomegaly, macrocephaly and IUGR for one, polymicrogyria on MRI for another - fetal MRI done because of FHx of affected child. (Unpublished data)\r\n\r\nLiu et al 2020 (PMID: 32848577) report one case with homozygous missense variants in this gene, who had focal cortical dysplasia and seizures from 3yo",
"entity_name": "DEPDC5",
"entity_type": "gene"
},
{
"created": "2022-08-11T14:16:22.601978Z",
"panel_name": "Fetal anomalies",
"panel_id": 478,
"panel_version": "1.900",
"user_name": "Rhiannon Mellis",
"item_type": "entity",
"text": "reviewed gene: DEPDC5: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 32848577; Phenotypes: Epilepsy, Structural brain malformations; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "DEPDC5",
"entity_type": "gene"
},
{
"created": "2022-08-11T14:08:10.810764Z",
"panel_name": "Fetal anomalies",
"panel_id": 478,
"panel_version": "1.900",
"user_name": "Rhiannon Mellis",
"item_type": "entity",
"text": "gene: ENG was added\ngene: ENG was added to Fetal anomalies. Sources: Expert Review,Literature\nMode of inheritance for gene: ENG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPhenotypes for gene: ENG were set to Telangiectasia, hereditary hemorrhagic, type 1\nReview for gene: ENG was set to AMBER\nAdded comment: This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs.\r\n\r\nClinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH).\r\n\r\nOutcome of review: May be fetally relevant but currently limited evidence, support adding to the Fetal anomalies panel as Amber gene.\r\n\r\nDetails of review:\r\nConsistency check because out of 4 known HHT genes EPHB4 and SMAD4 are on the fetal anomalies panel but ACVRL1 and ENG are not.\r\n\r\nNo specific published reports of ENG variants detected prenatally but correlates with pulmonary AVMs which can present neonatally and can be detected on prenatal US (PMID: 17719943; PMID: 21988128). \nSources: Expert Review, Literature",
"entity_name": "ENG",
"entity_type": "gene"
},
{
"created": "2022-08-11T14:05:37.683107Z",
"panel_name": "Fetal anomalies",
"panel_id": 478,
"panel_version": "1.900",
"user_name": "Rhiannon Mellis",
"item_type": "entity",
"text": "reviewed gene: ACVRL1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 27381467, 32170914; Phenotypes: Telangiectasia, hereditary hemorrhagic, type 2; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "ACVRL1",
"entity_type": "gene"
},
{
"created": "2022-08-11T14:00:43.587930Z",
"panel_name": "Fetal anomalies",
"panel_id": 478,
"panel_version": "1.900",
"user_name": "Rhiannon Mellis",
"item_type": "entity",
"text": "reviewed gene: TK2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial DNA depletion syndrome 2; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "TK2",
"entity_type": "gene"
},
{
"created": "2022-08-11T13:54:17.584608Z",
"panel_name": "Fetal anomalies",
"panel_id": 478,
"panel_version": "1.900",
"user_name": "Rhiannon Mellis",
"item_type": "entity",
"text": "gene: PIGS was added\ngene: PIGS was added to Fetal anomalies. Sources: Expert Review,Literature\nMode of inheritance for gene: PIGS was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: PIGS were set to PMID: 30269814\nPhenotypes for gene: PIGS were set to Developmental and epileptic encephalopathy 95\nReview for gene: PIGS was set to AMBER\nAdded comment: This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs.\r\n\r\nClinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH).\r\n\r\nOutcome of review: May be fetally relevant but currently limited evidence, support adding to the Fetal anomalies panel as Amber gene.\r\n\r\nDetails of review:\r\nCurrently red/amber on some other panels but reviewed on Congenital disorders of glycosylation panel as having sufficient evidence for green rating at next major review, in light of this same paper (PMID: 30269814). Three unrelated families reported. Severe neurological phenotype ranging from fetal akinesia to intellectual disability/epileptic encephalopathy. Fetal akinesia phenotype may be relevant for fetal anomalies panel. \nSources: Expert Review, Literature",
"entity_name": "PIGS",
"entity_type": "gene"
},
{
"created": "2022-08-11T13:09:14.527194Z",
"panel_name": "Fetal anomalies",
"panel_id": 478,
"panel_version": "1.900",
"user_name": "Rhiannon Mellis",
"item_type": "entity",
"text": "gene: MRPS16 was added\ngene: MRPS16 was added to Fetal anomalies. Sources: Expert Review,Literature\nMode of inheritance for gene: MRPS16 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: MRPS16 were set to PMID: 28749478\nPhenotypes for gene: MRPS16 were set to Combined oxidative phosphorylation deficiency 2\nReview for gene: MRPS16 was set to AMBER\nAdded comment: This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs.\r\n\r\nClinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH).\r\n\r\nOutcome of review: May be fetally relevant but currently limited evidence, support adding to the Fetal anomalies panel as Amber gene.\r\n\r\nDetails of review:\r\nAmber on mitochondrial/inborn errors of metabolism etc. Not Green on any panel. One previous case reported with \"agenesis of the corpus callosum, dysmorphism, and fatal neonatal lactic acidosis. The patient was small at birth, with dysmorphic facies, low-set ears, nonpitting edema of the limbs, brachydactyly, and redundant skin over the neck. She died of intractable metabolic acidosis at age 3 days.\" PMID:15505824 (2004). \r\n\r\nOne further fetal case reported by Shamseldin et al. 2018 (PMID: 28749478) with hydrops, very short long bones, and partial ACC \nSources: Expert Review, Literature",
"entity_name": "MRPS16",
"entity_type": "gene"
},
{
"created": "2022-08-11T13:05:21.861964Z",
"panel_name": "Fetal anomalies",
"panel_id": 478,
"panel_version": "1.900",
"user_name": "Rhiannon Mellis",
"item_type": "entity",
"text": "gene: THSD1 was added\ngene: THSD1 was added to Fetal anomalies. Sources: Expert Review,Literature\nMode of inheritance for gene: THSD1 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: THSD1 were set to PMID: 28749478; 26036949\nPhenotypes for gene: THSD1 were set to Intracerebral aneurysms; ?Hydrops fetalis\nReview for gene: THSD1 was set to AMBER\nAdded comment: This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs.\r\n\r\nClinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH).\r\n\r\nOutcome of review: May be fetally relevant but currently limited evidence, support adding to the Fetal anomalies panel as Amber gene pending more evidence.\r\n\r\nDetails of review:\r\nNot currently Green on any panels. Amber on Cerebral vascular malformations. (Heterozygous mutations identified in nine families with intracerebral aneurysms plus animal models but unclear on penetrance.) \r\n\r\nShamseldin et al 2018 (PMID: 28749478) report a fetal case with hydrops and a HOMOZYGOUS likely pathogenic variant in THSD1. The same group previously identified this same founder mutation in THSD1 in another 3 families with hydrops/oedema (PMID: 26036949) \nSources: Expert Review, Literature",
"entity_name": "THSD1",
"entity_type": "gene"
},
{
"created": "2022-08-11T13:03:19.844245Z",
"panel_name": "White matter disorders and cerebral calcification - narrow panel",
"panel_id": 476,
"panel_version": "1.241",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "Entity copied from Intellectual disability v3.1672",
"entity_name": "SLC35B2",
"entity_type": "gene"
},
{
"created": "2022-08-11T13:03:19.744844Z",
"panel_name": "White matter disorders and cerebral calcification - narrow panel",
"panel_id": 476,
"panel_version": "1.241",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "gene: SLC35B2 was added\ngene: SLC35B2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature,Expert Review Amber\nMode of inheritance for gene: SLC35B2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SLC35B2 were set to 35325049\nPhenotypes for gene: SLC35B2 were set to Abnormality of the skeletal system; Short long bone; Short stature; Abnormality of epiphysis morphology; Scoliosis; Multiple joint dislocation; Global develpmental delay; Intellectual disability; CNS hypomyelination; Abnormality of the corpus callosum; Cerebral atrophy; Abnormality of the amniotic fluid\nPenetrance for gene: SLC35B2 were set to Complete",
"entity_name": "SLC35B2",
"entity_type": "gene"
},
{
"created": "2022-08-11T13:03:13.945442Z",
"panel_name": "Skeletal dysplasia",
"panel_id": 309,
"panel_version": "2.211",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "Entity copied from Intellectual disability v3.1672",
"entity_name": "SLC35B2",
"entity_type": "gene"
},
{
"created": "2022-08-11T13:03:13.793378Z",
"panel_name": "Skeletal dysplasia",
"panel_id": 309,
"panel_version": "2.211",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "gene: SLC35B2 was added\ngene: SLC35B2 was added to Skeletal dysplasia. Sources: Literature,Expert Review Amber\nMode of inheritance for gene: SLC35B2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SLC35B2 were set to 35325049\nPhenotypes for gene: SLC35B2 were set to Abnormality of the skeletal system; Short long bone; Short stature; Abnormality of epiphysis morphology; Scoliosis; Multiple joint dislocation; Global develpmental delay; Intellectual disability; CNS hypomyelination; Abnormality of the corpus callosum; Cerebral atrophy; Abnormality of the amniotic fluid\nPenetrance for gene: SLC35B2 were set to Complete",
"entity_name": "SLC35B2",
"entity_type": "gene"
},
{
"created": "2022-08-11T12:51:31.864988Z",
"panel_name": "Intellectual disability",
"panel_id": 285,
"panel_version": "3.1672",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "Classified gene: SLC35B2 as Amber List (moderate evidence)",
"entity_name": "SLC35B2",
"entity_type": "gene"
},
{
"created": "2022-08-11T12:51:31.858788Z",
"panel_name": "Intellectual disability",
"panel_id": 285,
"panel_version": "3.1672",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "Added comment: Comment on list classification: The evidence for this gene is sufficient for an amber rating. Although supportive functional evidence is presented in PMID: 35325049, the presence of other variants in both cases reported in this article, means that further evidence is required for SLC35B2 to be rated Green.",
"entity_name": "SLC35B2",
"entity_type": "gene"
},
{
"created": "2022-08-11T12:51:31.801645Z",
"panel_name": "Intellectual disability",
"panel_id": 285,
"panel_version": "3.1672",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "Gene: slc35b2 has been classified as Amber List (Moderate Evidence).",
"entity_name": "SLC35B2",
"entity_type": "gene"
},
{
"created": "2022-08-11T12:32:27.282966Z",
"panel_name": "Fetal anomalies",
"panel_id": 478,
"panel_version": "1.900",
"user_name": "Rhiannon Mellis",
"item_type": "entity",
"text": "gene: MYBPC3 was added\ngene: MYBPC3 was added to Fetal anomalies. Sources: Expert Review,Literature\nMode of inheritance for gene: MYBPC3 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal\nPublications for gene: MYBPC3 were set to PMID: 28749478; 19858127\nPhenotypes for gene: MYBPC3 were set to Cardiomyopathy; ?Congenital myopathy\nReview for gene: MYBPC3 was set to AMBER\nAdded comment: This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs.\r\n\r\nClinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH).\r\n\r\nOutcome of review: May be fetally relevant but currently limited evidence, support adding to the Fetal anomalies panel as Amber gene pending more evidence.\r\n\r\nCurrently rated Green on the following other PanelApp panel(s): Various cardiomyopathy panels. Amber on congenital myopathy panel.\r\n\r\nDetails of review:\r\nPreviously only one (AR) case with skeletal muscle phenotype, although is a known cardiomyopathy gene (PMID: 19858127). One fetal case reported by Shamseldin et al 2018 (PMID: 28749478) with hydrops. \nSources: Expert Review, Literature",
"entity_name": "MYBPC3",
"entity_type": "gene"
},
{
"created": "2022-08-11T12:24:45.599592Z",
"panel_name": "Fetal anomalies",
"panel_id": 478,
"panel_version": "1.900",
"user_name": "Rhiannon Mellis",
"item_type": "entity",
"text": "reviewed gene: NUP88: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 33060286; Phenotypes: fetal akinesia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "NUP88",
"entity_type": "gene"
},
{
"created": "2022-08-11T12:20:16.254619Z",
"panel_name": "Genetic epilepsy syndromes",
"panel_id": 402,
"panel_version": "2.569",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "Tag Q3_22_NHS_review tag was added to gene: CERS1.",
"entity_name": "CERS1",
"entity_type": "gene"
},
{
"created": "2022-08-11T12:20:06.418346Z",
"panel_name": "Fetal anomalies",
"panel_id": 478,
"panel_version": "1.900",
"user_name": "Rhiannon Mellis",
"item_type": "entity",
"text": "gene: CACNA1S was added\ngene: CACNA1S was added to Fetal anomalies. Sources: Expert Review,Literature\nMode of inheritance for gene: CACNA1S was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: CACNA1S were set to PMID: 33060286; 28012042\nPhenotypes for gene: CACNA1S were set to Congenital myopathy; arthrogryposis\nReview for gene: CACNA1S was set to AMBER\nAdded comment: This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs.\r\n\r\nClinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH).\r\n\r\nOutcome of review: May be fetally relevant but currently limited evidence, support adding to the Fetal anomalies panel as Amber gene.\r\n\r\nDetails of review:\r\nPreviously only monoallelic variants reported associated with malignant hyperthermia and periodic paralysis but more recently biallelic variants have been associated with congenital myopathy. In Ravenscroft et al 2020 (PMID: 33060286) the reported biallelic variants were VUS but strong suspicion of causality: the proband had polyhydramnios, scalp oedema, bilateral wrist contractures, bilateral talipes and reduced fetal movements, ToP at 26/40. Mild facial dysmorphic features were noted on autopsy, including low anterior hairline, mild hypertelorism and moderate retrognathia. A previous pregnancy was affected with polyhydramnios and reduced fetal movements, delivered at 32/40 due to placental abruption and died at 10 days. On photos the baby had ptosis and broad nasal tip. The biallelic variants segregated within the family (parents and the 2 unaffected sibs all het). No cell lines available for functional studies.\r\nAnother study (PMID: 28012042) reports 7 families with congenital myopathy and CACNA1S mutations (both recessive and dominant), of whom 3 had cases with antenatal onset (reduced fetal movements). \nSources: Expert Review, Literature",
"entity_name": "CACNA1S",
"entity_type": "gene"
},
{
"created": "2022-08-11T12:18:05.717696Z",
"panel_name": "Genetic epilepsy syndromes",
"panel_id": 402,
"panel_version": "2.569",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "Phenotypes for gene: FAR1 were changed from Peroxisomal fatty acyl-CoA reductase 1 disorder, OMIM:616154 to Peroxisomal fatty acyl-CoA reductase 1 disorder, OMIM:616154; fatty acyl-CoA reductase 1 deficiency, MONDO:0014510",
"entity_name": "FAR1",
"entity_type": "gene"
},
{
"created": "2022-08-11T12:12:57.738816Z",
"panel_name": "Genetic epilepsy syndromes",
"panel_id": 402,
"panel_version": "2.568",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "Tag Q3_22_NHS_review tag was added to gene: FAR1.",
"entity_name": "FAR1",
"entity_type": "gene"
},
{
"created": "2022-08-11T11:03:08.845991Z",
"panel_name": "Fetal anomalies",
"panel_id": 478,
"panel_version": "1.900",
"user_name": "Rhiannon Mellis",
"item_type": "entity",
"text": "gene: NDUFB10 was added\ngene: NDUFB10 was added to Fetal anomalies. Sources: Expert Review,Literature\nMode of inheritance for gene: NDUFB10 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: NDUFB10 were set to PMID: 31130284; 28040730\nPhenotypes for gene: NDUFB10 were set to Mitochondrial complex I deficiency\nReview for gene: NDUFB10 was set to AMBER\nAdded comment: This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs.\r\n\r\nClinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH).\r\n\r\nOutcome of review: May be fetally relevant but currently limited evidence, support adding to the Fetal anomalies panel as Amber gene.\r\n\r\nDetails of review:\r\nNot Green on any other panels (Amber/Red because only 1 case reported, with functional studies). Causes Mitochondrial complex 1 deficiency. \r\nOne fetal case reported by Monies et al 2019 (PMID: 31130284) with Non-immune hydrops fetalis and died after birth. \r\nThe previous reported case on OMIM (from PMID: 28040730) was a female infant with IUGR, hydrops, lung hypoplasia and fetal cardiomyopathy - neonatal death with rapidly progressive lactic acidosis and PM found decreased complex 1 activity in skeletal muscle, heart, liver. Previous child of parents also had hydrops and died on day 1 of life. \nSources: Expert Review, Literature",
"entity_name": "NDUFB10",
"entity_type": "gene"
},
{
"created": "2022-08-11T10:58:39.957195Z",
"panel_name": "Fetal anomalies",
"panel_id": 478,
"panel_version": "1.900",
"user_name": "Rhiannon Mellis",
"item_type": "entity",
"text": "gene: FTO was added\ngene: FTO was added to Fetal anomalies. Sources: Expert Review,Literature\nMode of inheritance for gene: FTO was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: FTO were set to PMID: 31130284; 19559399; 26378117\nPhenotypes for gene: FTO were set to Growth retardation, developmental delay, facial dysmorphism\nReview for gene: FTO was set to AMBER\nAdded comment: This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs.\r\n\r\nClinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH).\r\n\r\nOutcome of review: May be fetally relevant but currently limited evidence, support adding to the Fetal anomalies panel as Amber gene.\r\n\r\nDetails of review:\r\nNot Green on any panels (only 2 families reported to date). On OMIM: Growth retardation, developmental delay, facial dysmorphism. One fetal case reported by Monies et al 2019 (PMID: 31130284) with Dandy-Walker malformation, IUGR, and polyhydramnios. This fits with the phenotype reported in one consanguineous family with 9 affected individuals reported by Boissel 2009 PMID: 19559399. The other reported case is PMID: 26378117 - a homozygous missense variant in FTO was identified in a 21-month old girl who presented with growth retardation, failure to thrive, severely delayed development, Dysmorphic facial features, decreased brain parenchyma, delayed myelination, and a thin corpus callosum. \nSources: Expert Review, Literature",
"entity_name": "FTO",
"entity_type": "gene"
},
{
"created": "2022-08-11T10:54:09.446584Z",
"panel_name": "Fetal anomalies",
"panel_id": 478,
"panel_version": "1.900",
"user_name": "Rhiannon Mellis",
"item_type": "entity",
"text": "reviewed gene: CACNA1D: Rating: ; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 32410215; Phenotypes: PRIMARY ALDOSTERONISM, SEIZURES, AND NEUROLOGIC ABNORMALITIES; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "CACNA1D",
"entity_type": "gene"
},
{
"created": "2022-08-11T10:33:09.975944Z",
"panel_name": "Genetic epilepsy syndromes",
"panel_id": 402,
"panel_version": "2.568",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "Publications for gene: CERS1 were set to 19243074; 30800706; 21625621; 24782409",
"entity_name": "CERS1",
"entity_type": "gene"
},
{
"created": "2022-08-11T10:12:14.912145Z",
"panel_name": "Genetic epilepsy syndromes",
"panel_id": 402,
"panel_version": "2.567",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "changed review comment from: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. Numerous variants have been reported in cases of McLeod syndrome with or without chronic granulomatous disease (OMIM:300842), including at least two cases in females; severe symptoms were apparent in the index case (11.1) who had marked skewed X-inactivation favouring the wild type allele (PMID: 8619554).; to: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. Numerous variants have been reported in cases of McLeod syndrome with or without chronic granulomatous disease (OMIM:300842), including at least two cases in females; severe symptoms were apparent in the index case (11.1) who had marked skewed X-inactivation favouring the wild type allele (PMID: 8619554). Generalized seizures are reported in 20-40% cases of McLeod syndrome with or without chronic granulomatous disease (OMIM:300842) according to OMIM.",
"entity_name": "XK",
"entity_type": "gene"
},
{
"created": "2022-08-11T10:06:55.664348Z",
"panel_name": "Genetic epilepsy syndromes",
"panel_id": 402,
"panel_version": "2.567",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "Deleted their comment",
"entity_name": "XK",
"entity_type": "gene"
},
{
"created": "2022-08-11T10:06:48.584221Z",
"panel_name": "Genetic epilepsy syndromes",
"panel_id": 402,
"panel_version": "2.567",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "Tag Q3_22_rating was removed from gene: XK.\nTag Q3_22_MOI was removed from gene: XK.",
"entity_name": "XK",
"entity_type": "gene"
},
{
"created": "2022-08-11T10:06:19.047906Z",
"panel_name": "Childhood onset dystonia or chorea or related movement disorder",
"panel_id": 847,
"panel_version": "1.246",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "Classified gene: XK as Amber List (moderate evidence)",
"entity_name": "XK",
"entity_type": "gene"
},
{
"created": "2022-08-11T10:06:19.043339Z",
"panel_name": "Childhood onset dystonia or chorea or related movement disorder",
"panel_id": 847,
"panel_version": "1.246",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.",
"entity_name": "XK",
"entity_type": "gene"
},
{
"created": "2022-08-11T10:06:19.015790Z",
"panel_name": "Childhood onset dystonia or chorea or related movement disorder",
"panel_id": 847,
"panel_version": "1.246",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "Gene: xk has been classified as Amber List (Moderate Evidence).",
"entity_name": "XK",
"entity_type": "gene"
},
{
"created": "2022-08-11T10:05:05.166244Z",
"panel_name": "Childhood onset dystonia or chorea or related movement disorder",
"panel_id": 847,
"panel_version": "1.245",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "Deleted their comment",
"entity_name": "XK",
"entity_type": "gene"
},
{
"created": "2022-08-11T10:04:24.085996Z",
"panel_name": "Genetic epilepsy syndromes",
"panel_id": 402,
"panel_version": "2.567",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "Entity copied from Childhood onset dystonia or chorea or related movement disorder v1.245",
"entity_name": "XK",
"entity_type": "gene"
},
{
"created": "2022-08-11T10:04:23.939268Z",
"panel_name": "Genetic epilepsy syndromes",
"panel_id": 402,
"panel_version": "2.567",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "gene: XK was added\ngene: XK was added to Genetic epilepsy syndromes. Sources: Expert list,Expert Review Amber\nQ3_22_rating, Q3_22_MOI tags were added to gene: XK.\nMode of inheritance for gene: XK was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)\nPublications for gene: XK were set to 11761473; 30128557; 8004674; 8619554\nPhenotypes for gene: XK were set to McLeod syndrome with or without chronic granulomatous disease, OMIM:300842; McLeod neuroacanthocytosis syndrome, MONDO:0018945",
"entity_name": "XK",
"entity_type": "gene"
},
{
"created": "2022-08-11T10:01:19.877786Z",
"panel_name": "Childhood onset dystonia or chorea or related movement disorder",
"panel_id": 847,
"panel_version": "1.245",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "Tag Q3_22_rating tag was added to gene: XK.\nTag Q3_22_MOI tag was added to gene: XK.",
"entity_name": "XK",
"entity_type": "gene"
},
{
"created": "2022-08-11T10:00:33.496775Z",
"panel_name": "Childhood onset dystonia or chorea or related movement disorder",
"panel_id": 847,
"panel_version": "1.245",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "Classified gene: XK as Amber List (moderate evidence)",
"entity_name": "XK",
"entity_type": "gene"
},
{
"created": "2022-08-11T10:00:33.493721Z",
"panel_name": "Childhood onset dystonia or chorea or related movement disorder",
"panel_id": 847,
"panel_version": "1.245",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.",
"entity_name": "XK",
"entity_type": "gene"
},
{
"created": "2022-08-11T10:00:33.450788Z",
"panel_name": "Childhood onset dystonia or chorea or related movement disorder",
"panel_id": 847,
"panel_version": "1.245",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "Gene: xk has been classified as Amber List (Moderate Evidence).",
"entity_name": "XK",
"entity_type": "gene"
},
{
"created": "2022-08-11T09:44:39.880772Z",
"panel_name": "Childhood onset dystonia or chorea or related movement disorder",
"panel_id": 847,
"panel_version": "1.244",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "Publications for gene: XK were set to 11761473; 30128557; 8004674",
"entity_name": "XK",
"entity_type": "gene"
},
{
"created": "2022-08-11T09:44:09.474460Z",
"panel_name": "Childhood onset dystonia or chorea or related movement disorder",
"panel_id": 847,
"panel_version": "1.243",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "reviewed gene: XK: Rating: GREEN; Mode of pathogenicity: None; Publications: 8619554; Phenotypes: ; Mode of inheritance: None",
"entity_name": "XK",
"entity_type": "gene"
},
{
"created": "2022-08-11T09:43:04.683315Z",
"panel_name": "Early onset dementia (encompassing fronto-temporal dementia and prion disease)",
"panel_id": 265,
"panel_version": "1.79",
"user_name": "Sarah Leigh",
"item_type": "entity",
"text": "reviewed gene: XK: Rating: GREEN; Mode of pathogenicity: None; Publications: 8619554; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)",
"entity_name": "XK",
"entity_type": "gene"
},
{
"created": "2022-08-11T09:27:53.969375Z",
"panel_name": "Fetal anomalies",
"panel_id": 478,
"panel_version": "1.900",
"user_name": "Rhiannon Mellis",
"item_type": "entity",
"text": "edited their review of gene: ASXL3: Added comment: This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs.\r\n\r\nClinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH).\r\n\r\nOutcome of review: May be fetally relevant but still limited evidence, support keeping as Amber gene for now.\r\n\r\nDetails of review:\r\nPreviously reviewed as Amber as 2 fetal cases in literature: one from PMID: 32565546 with short CC and metopic synostosis, one from PMID: 29316359 with distal arthrogryposis and cerebellar vermian hypoplasia. Now there is one more fetal case reported with arthrogryposis - PMID: 33820833; Changed publications to: PMID: 33820833; Changed phenotypes to: Arthrogryposis",
"entity_name": "ASXL3",
"entity_type": "gene"
}
]
}