HTTP 200 OK
Allow: GET, HEAD, OPTIONS
Content-Type: application/json
Vary: Accept
{
"count": 221304,
"next": "https://panelapp-aus.org/api/v1/activities/?format=api&page=1754",
"previous": "https://panelapp-aus.org/api/v1/activities/?format=api&page=1752",
"results": [
{
"created": "2020-07-01T15:23:42.395225+10:00",
"panel_name": "Aortopathy_Connective Tissue Disorders",
"panel_id": 44,
"panel_version": "0.100",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Classified gene: B3GALT6 as Green List (high evidence)",
"entity_name": "B3GALT6",
"entity_type": "gene"
},
{
"created": "2020-07-01T15:23:42.381235+10:00",
"panel_name": "Aortopathy_Connective Tissue Disorders",
"panel_id": 44,
"panel_version": "0.100",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Gene: b3galt6 has been classified as Green List (High Evidence).",
"entity_name": "B3GALT6",
"entity_type": "gene"
},
{
"created": "2020-07-01T15:23:13.396743+10:00",
"panel_name": "Aortopathy_Connective Tissue Disorders",
"panel_id": 44,
"panel_version": "0.99",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "gene: B3GALT6 was added\ngene: B3GALT6 was added to Aortopathy_Connective Tissue Disorders. Sources: Expert list\nMode of inheritance for gene: B3GALT6 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: B3GALT6 were set to 29931299; 28306229\nPhenotypes for gene: B3GALT6 were set to Ehlers Danlos syndrome, progeroid type, 2, 615349; Spondylodysplastic EDS\nReview for gene: B3GALT6 was set to GREEN\nAdded comment: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229).\r\nIn 12 patients from 9 families with EDSSPD2, 8 compound heterozygous mutations and 1 homozygous mutation in B3GALT6 were identified, including 11 missense variants, 2 frameshift variants, a deletion of 19 amino acids, and a start codon alteration (PMID: 29931299). \nSources: Expert list",
"entity_name": "B3GALT6",
"entity_type": "gene"
},
{
"created": "2020-07-01T15:17:52.359953+10:00",
"panel_name": "Aortopathy_Connective Tissue Disorders",
"panel_id": 44,
"panel_version": "0.98",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Marked gene: ADAMTS2 as ready",
"entity_name": "ADAMTS2",
"entity_type": "gene"
},
{
"created": "2020-07-01T15:17:52.348744+10:00",
"panel_name": "Aortopathy_Connective Tissue Disorders",
"panel_id": 44,
"panel_version": "0.98",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Gene: adamts2 has been classified as Green List (High Evidence).",
"entity_name": "ADAMTS2",
"entity_type": "gene"
},
{
"created": "2020-07-01T15:17:23.628032+10:00",
"panel_name": "Aortopathy_Connective Tissue Disorders",
"panel_id": 44,
"panel_version": "0.98",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Publications for gene: ADAMTS2 were set to PMID: 30071989; 26765342",
"entity_name": "ADAMTS2",
"entity_type": "gene"
},
{
"created": "2020-07-01T15:16:49.170957+10:00",
"panel_name": "Aortopathy_Connective Tissue Disorders",
"panel_id": 44,
"panel_version": "0.97",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Classified gene: ADAMTS2 as Green List (high evidence)",
"entity_name": "ADAMTS2",
"entity_type": "gene"
},
{
"created": "2020-07-01T15:16:49.165150+10:00",
"panel_name": "Aortopathy_Connective Tissue Disorders",
"panel_id": 44,
"panel_version": "0.97",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Added comment: Comment on list classification: One of the 19 EDS genes recognised by the International EDS Consortium (PMID: 28306229)",
"entity_name": "ADAMTS2",
"entity_type": "gene"
},
{
"created": "2020-07-01T15:16:49.131682+10:00",
"panel_name": "Aortopathy_Connective Tissue Disorders",
"panel_id": 44,
"panel_version": "0.97",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Gene: adamts2 has been classified as Green List (High Evidence).",
"entity_name": "ADAMTS2",
"entity_type": "gene"
},
{
"created": "2020-07-01T13:48:07.399054+10:00",
"panel_name": "Aortopathy_Connective Tissue Disorders",
"panel_id": 44,
"panel_version": "0.96",
"user_name": "Paul De Fazio",
"item_type": "entity",
"text": "gene: NOTCH1 was added\ngene: NOTCH1 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature\nMode of inheritance for gene: NOTCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: NOTCH1 were set to 16729972; 26820064; 16025100; 25963545\nPhenotypes for gene: NOTCH1 were set to Aortic valve disease MIM# 109730\nReview for gene: NOTCH1 was set to GREEN\nAdded comment: NOTCH1 variants are associated with cardiac abnormalities including aortic valve stenosis, a bicuspid aortic valve, coarctation of the aorta, hypoplastic left heart syndrome, and thoracic aortic aneurysms in nonsyndromic individuals (2 families in PMID:16025100; 2 individuals in PMID:16729972; 14 families in PMID:26820064). Penetrance is incomplete and not all individuals display all phenotypes (e.g. only 6/63 individuals from PMID:26820064 had thoracic aortic aneurysms).\r\n\r\nMonoallelic NOTCH1 variants are also responsible for Adams-Oliver syndrome, which can have associated cardiac abnormalities (PMID: 25963545). \nSources: Literature",
"entity_name": "NOTCH1",
"entity_type": "gene"
},
{
"created": "2020-07-01T13:20:16.807788+10:00",
"panel_name": "Aortopathy_Connective Tissue Disorders",
"panel_id": 44,
"panel_version": "0.96",
"user_name": "Paul De Fazio",
"item_type": "entity",
"text": "gene: TNXB was added\ngene: TNXB was added to Aortopathy_Connective Tissue Disorders. Sources: Literature\nMode of inheritance for gene: TNXB was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: TNXB were set to 28306229; 28306225; 23620400\nPhenotypes for gene: TNXB were set to Ehlers-Danlos syndrome, classic-like, 1 MIM# 606408\nReview for gene: TNXB was set to GREEN\ngene: TNXB was marked as current diagnostic\nAdded comment: Association with classic Ehlers-Danlos syndrome is well-established (PMID:28306229;28306225).\r\n\r\nTwo families have also been described with Vesicoureteral Reflux caused by a heterozygous missense variant in this gene, some individuals were reported with asymptomatic joint hypermobility (PMID:23620400) \nSources: Literature",
"entity_name": "TNXB",
"entity_type": "gene"
},
{
"created": "2020-07-01T13:17:52.303235+10:00",
"panel_name": "Aortopathy_Connective Tissue Disorders",
"panel_id": 44,
"panel_version": "0.96",
"user_name": "Paul De Fazio",
"item_type": "entity",
"text": "gene: PLOD1 was added\ngene: PLOD1 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature\nMode of inheritance for gene: PLOD1 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: PLOD1 were set to 28306225; 28306229\nPhenotypes for gene: PLOD1 were set to Ehlers-Danlos syndrome, kyphoscoliotic type, MIM# 225400\nReview for gene: PLOD1 was set to GREEN\ngene: PLOD1 was marked as current diagnostic\nAdded comment: Review in PMID: 28306225 states: \"A total of 139 mutations in PLOD1 have been identified in the 84 confirmed cases, of these there are 39 different mutations.\" It is included in The 2017 International Classification of the Ehlers-Danlos Syndromes (PMID: 28306229).\r\n\r\nMedium‐sized vessel rupture has been reported in several individual case reports. \nSources: Literature",
"entity_name": "PLOD1",
"entity_type": "gene"
},
{
"created": "2020-07-01T13:15:13.243689+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.35",
"user_name": "Elena Savva",
"item_type": "entity",
"text": "gene: GAA was added\ngene: GAA was added to Limb Girdle Muscular Dystrophy. Sources: Expert list\nMode of inheritance for gene: GAA was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: GAA were set to PMID: 29880332\nPhenotypes for gene: GAA were set to Glycogen storage disease II\t232300\nReview for gene: GAA was set to GREEN\nAdded comment: PMID: 29880332 - 16 adult patients (9 families) with Pombe disease. Proximal muscle weakness (12/16) and elevated CK were reported. Muscle biopsy showed vacuoles in 4/9 patients. Patients were described as having LGMD. \nSources: Expert list",
"entity_name": "GAA",
"entity_type": "gene"
},
{
"created": "2020-07-01T13:12:07.651284+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.35",
"user_name": "Crystle Lee",
"item_type": "entity",
"text": "gene: GNE was added\ngene: GNE was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review\nMode of inheritance for gene: GNE was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: GNE were set to 22883483\nPhenotypes for gene: GNE were set to Nonaka myopathy (MIM#605820)\nReview for gene: GNE was set to AMBER\nAdded comment: Primarily a distal myopathy however proximal muscle weakness have also been reported. Limited evidence supporting LGMD phenotype. \r\n\r\nPMID: 22883483: Half the patients reported with LGMD type proximal muscle weakness. \nSources: Expert Review",
"entity_name": "GNE",
"entity_type": "gene"
},
{
"created": "2020-07-01T12:57:57.345710+10:00",
"panel_name": "Aortopathy_Connective Tissue Disorders",
"panel_id": 44,
"panel_version": "0.96",
"user_name": "Paul De Fazio",
"item_type": "entity",
"text": "gene: SLC39A13 was added\ngene: SLC39A13 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature\nMode of inheritance for gene: SLC39A13 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SLC39A13 were set to 18985159; 18513683; 28306229; 28306225\nPhenotypes for gene: SLC39A13 were set to Ehlers-Danlos syndrome, spondylodysplastic type, MIM# 612350\nReview for gene: SLC39A13 was set to GREEN\ngene: SLC39A13 was marked as current diagnostic\nAdded comment: 3 unrelated families described to date (PMID: 18985159;18513683). Is included in The 2017 International Classification of the Ehlers-Danlos Syndromes (PMID: 28306229). See PMID: 28306225 for a review. \nSources: Literature",
"entity_name": "SLC39A13",
"entity_type": "gene"
},
{
"created": "2020-07-01T12:55:30.128315+10:00",
"panel_name": "Aortopathy_Connective Tissue Disorders",
"panel_id": 44,
"panel_version": "0.96",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "gene: ALDH18A1 was added\ngene: ALDH18A1 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature\nMode of inheritance for gene: ALDH18A1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal\nPublications for gene: ALDH18A1 were set to PMID: 30071989; 26320891; 24913064; 18478038; 21739576; 22411858; 28228640\nPhenotypes for gene: ALDH18A1 were set to Cutis laxa, autosomal dominant 3 (MIM# 616603); Cutis laxa, autosomal recessive, type IIIA (MIM# 219150)\nReview for gene: ALDH18A1 was set to GREEN\nAdded comment: PMID: 30071989; not a HTAAD gene by clingen working group\r\n\r\nCutis laxa, autosomal dominant 3 (MIM# 616603)\r\n\r\nPMID: 28228640;\r\n- Born to consanguineous parents and harbour a de novo missense p.(Arg126His). no functional done\r\n\r\nPMID: 26320891; \r\n- 8 unrelated individuals born to non-consanguineous families clinically diagnosed with de-barsy syndrome (DBS) or wrinkly skin syndrome. All variants occur at codon Arg138 and parental DNA from 6 probands confirmed de novo origin. (NOTE: table 1 states paternal origin however this is referring to the allele not variant (Figure S1)).\r\n- Imaging of patients's cells showed increased accumulation of mutant protein at the mitochondrial outer membrane.\r\n- Biochemical studies using patients' fibroblasts demonstrated LoF\r\n\r\n\r\nCutis laxa, autosomal recessive, type IIIA (MIM# 219150)\r\n\r\nPMID: 24913064;\r\n- 2 patients from consanguineous families, 1x fs (c.2131del)+ 1x 1522bp del (resulting in exon 15 del)\r\n- clinical features like facial dysmorphism, hypotonia, adducted thumbs and cutis laxa, which are frequently found in progeroid cutis laxa syndromes. In addition, they had cardiovascular abnormalities\r\n\r\nPMID: 18478038;\r\n- missense c.2350C>T; p.(His784Tyr) found in a a consanguineous New Zealand Maori family with 4 affecteds.\r\n- patients' fibroblasts showed no defect in Proline accumulation\r\n\r\nPMID: 21739576;\r\nThis severely affected child, born to consanguineous parents of Pakistani origin, presented with lax, wrinkled and thin skin with dilated and tortuous subcutaneous blood vessels, corneal clouding, and hypotonia. The child had severe global developmental delay and feeding difficulties and died in infancy for an unknown reason. The proband was homozygous for a mutation in ALDH18A1 , c.1923 + 1G > A\r\n\r\nPMID: 22411858;\r\npair of siblings chet for p.(Ser742Ile) and p.(Arg425Cys) \nSources: Literature",
"entity_name": "ALDH18A1",
"entity_type": "gene"
},
{
"created": "2020-07-01T12:49:06.886542+10:00",
"panel_name": "Aortopathy_Connective Tissue Disorders",
"panel_id": 44,
"panel_version": "0.96",
"user_name": "Paul De Fazio",
"item_type": "entity",
"text": "gene: SMAD6 was added\ngene: SMAD6 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature\nMode of inheritance for gene: SMAD6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: SMAD6 were set to 22275001; 28659821; 30963242; 30848080; 30796334\nPhenotypes for gene: SMAD6 were set to Aortic valve disease 2 MIM# 614823\nReview for gene: SMAD6 was set to AMBER\ngene: SMAD6 was marked as current diagnostic\nAdded comment: Missense and LOF SMAD6 variants described as pathogenic or likely pathogenic have been identified in at least 20 individuals from bicuspid aortic valve/nonsyndromic thoracic aortic aneurysm cohorts (PMID:22275001, 30848080, 28659821, 30796334).\r\n\r\nFunctional studies on two of the missense variants supported abnormal function, but a third variant did not show any functional defect (and was also not well-conserved) (PMID:22275001).\r\n\r\nFamilial segregation studies in PMID: 30796334 demonstrated reduced penetrance (82%) and variable clinical expressivity, with coarctation of the aorta being a common comorbidity. \r\n\r\nBiallelic variants have been decribed in 2 individuals with 'complex cardiac phenotype' (including aortic isthmus stenosis, dysplastic and stenotic pulmonary valve, and dilated cardiomyopathy) (PMID: 30963242).\r\n\r\nThere appears to be a clear gene-disease relationship but I am not sure if it belongs in this panel. \nSources: Literature",
"entity_name": "SMAD6",
"entity_type": "gene"
},
{
"created": "2020-07-01T12:45:27.576498+10:00",
"panel_name": "Arthrogryposis",
"panel_id": 47,
"panel_version": "0.65",
"user_name": "Elena Savva",
"item_type": "entity",
"text": "gene: FLNC was added\ngene: FLNC was added to Arthrogryposis. Sources: Literature\nMode of inheritance for gene: FLNC was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: FLNC were set to PMID: 29858533\nPhenotypes for gene: FLNC were set to Cardiomyopathy, familial restrictive 5\t617047; Myopathy, distal, 4\t614065; Myopathy, myofibrillar, 5\t609524\nMode of pathogenicity for gene: FLNC was set to Other\nReview for gene: FLNC was set to GREEN\nAdded comment: Myofibrillar myopathy - LOF\r\nDistal myopathy - GOF\r\nCardiomyopathy, familial hypertrophic - LOF PTCs\r\n\r\nPMID: 29858533 - 4 patients with both restrictive cardiomyopathy and congenital myopathy. 4/4 displayed limb girdle muscle weakness, where 1/4 was mild.\r\n3/4 also presented with arthrogryposis \nSources: Literature",
"entity_name": "FLNC",
"entity_type": "gene"
},
{
"created": "2020-07-01T12:44:50.870885+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.35",
"user_name": "Elena Savva",
"item_type": "entity",
"text": "gene: FLNC was added\ngene: FLNC was added to Limb Girdle Muscular Dystrophy. Sources: Expert list\nMode of inheritance for gene: FLNC was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: FLNC were set to PMID: 29858533\nPhenotypes for gene: FLNC were set to Cardiomyopathy, familial restrictive 5\t617047; Myopathy, distal, 4\t614065; Myopathy, myofibrillar, 5\t609524\nMode of pathogenicity for gene: FLNC was set to Other\nReview for gene: FLNC was set to GREEN\nAdded comment: Myofibrillar myopathy - LOF\r\nDistal myopathy - GOF\r\nCardiomyopathy, familial hypertrophic - LOF PTCs\r\n\r\nPMID: 29858533 - 4 patients with both restrictive cardiomyopathy and congenital myopathy. 4/4 displayed limb girdle muscle weakness, where 1/4 was mild. \r\n3/4 also presented with arthrogryposis \nSources: Expert list",
"entity_name": "FLNC",
"entity_type": "gene"
},
{
"created": "2020-07-01T12:41:04.174545+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.35",
"user_name": "Crystle Lee",
"item_type": "entity",
"text": "gene: LAMP2 was added\ngene: LAMP2 was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review\nMode of inheritance for gene: LAMP2 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: LAMP2 were set to 27179547; 22541782\nPhenotypes for gene: LAMP2 were set to Danon disease (MIM#300257)\nReview for gene: LAMP2 was set to AMBER\nAdded comment: Primarily presents as a cardiomyopathy condition, skeletal myopathy is less prominent and generally mild. Phenotypic overlap, proximal muscle weakness (85% of patients) (OMIM)\r\n\r\nPMID: 27179547: 2 out of 7 affected members of 1 family presented with LGMD. \r\n\r\nPMID: 22541782: Reported 2 patients. 1 patient presented with LGMD phenotype. EMG showed myopathic changes. \nSources: Expert Review",
"entity_name": "LAMP2",
"entity_type": "gene"
},
{
"created": "2020-07-01T12:29:55.224722+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.35",
"user_name": "Elena Savva",
"item_type": "entity",
"text": "gene: ETFDH was added\ngene: ETFDH was added to Limb Girdle Muscular Dystrophy. Sources: Expert list\nMode of inheritance for gene: ETFDH was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: ETFDH were set to PMID: 19592060; 17412732\nPhenotypes for gene: ETFDH were set to Glutaric acidemia IIC\t231680\nReview for gene: ETFDH was set to AMBER\nAdded comment: PMID: 19592060 - 1 adult patient reported with weakness in pelvic girdle muscles\r\n\r\nPMID: 17412732 - 7 patients (5 families) with exercise intolerance and proximal myopathy with elevated CK levels. Onset ranged from childhood to adult-onset. Muscle histology in all five index cases revealed similar findings: moderate to severe myopathy with small vacuoles in most type 1 fibres. Patient also had subacute (3–6 months) exercise intolerance and proximal weakness affecting predominantly hip and shoulder girdle muscles. \nSources: Expert list",
"entity_name": "ETFDH",
"entity_type": "gene"
},
{
"created": "2020-07-01T12:09:08.288080+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.35",
"user_name": "Elena Savva",
"item_type": "entity",
"text": "gene: DOK7 was added\ngene: DOK7 was added to Limb Girdle Muscular Dystrophy. Sources: Expert list\nMode of inheritance for gene: DOK7 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: DOK7 were set to PMID: 31453852; 32360404\nPhenotypes for gene: DOK7 were set to Myasthenic syndrome, congenital, 10\t254300\nReview for gene: DOK7 was set to GREEN\nAdded comment: PMID: 31453852 - two adult patients with PTC variants and severe proximal muscle weakness with childhood onset. Condition is described as limb girdle myasthenia. Patient 1 had shoulder abduction and severe weakness of the pelvic girdle, patient 2 had muscle biopsy reveal muscle fibre II atrophy.\r\n\r\nPMID: 32360404 - one adult patient with late onset atypical limb-girdle pattern of muscle weakness. Biopsy of deltoid muscle shows no features of MD.\r\n\r\nPMID: 18626973 - 16 patients report proximal limb weakness, where 10 report neonatal onset. \nSources: Expert list",
"entity_name": "DOK7",
"entity_type": "gene"
},
{
"created": "2020-07-01T11:30:33.764532+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.35",
"user_name": "Crystle Lee",
"item_type": "entity",
"text": "gene: LMNA was added\ngene: LMNA was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review\nMode of inheritance for gene: LMNA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: LMNA were set to 27220833; 23746545; 17377071\nPhenotypes for gene: LMNA were set to Emery-Dreifuss muscular dystrophy 2, autosomal dominant\t(MIM#181350)\nMode of pathogenicity for gene: LMNA was set to Other\nReview for gene: LMNA was set to AMBER\nAdded comment: Phenotypic overlap, Formerly known as Limb-girdle muscular dystrophy 1B (LGMD1B) but has been reclassified as EDMD (OMIM) \r\n\r\nPMID: 27220833: 1 late onset patient with LGMD\r\n\r\nPMID: 23746545: Late onset patient with severe LGMD\r\n\r\nPMID: 17377071: Later onset phenotypes may be associated with LoF while dominant negative variants result in childhood onset disease \nSources: Expert Review",
"entity_name": "LMNA",
"entity_type": "gene"
},
{
"created": "2020-07-01T11:23:06.242513+10:00",
"panel_name": "Aortopathy_Connective Tissue Disorders",
"panel_id": 44,
"panel_version": "0.96",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "gene: ADAMTS2 was added\ngene: ADAMTS2 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature\nMode of inheritance for gene: ADAMTS2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: ADAMTS2 were set to PMID: 30071989; 26765342\nPhenotypes for gene: ADAMTS2 were set to Ehlers-Danlos syndrome, dermatosparaxis type (MIM# 225410)\nReview for gene: ADAMTS2 was set to GREEN\nAdded comment: PMID: 30071989; not a gene for HTAAD by Clingen working group\r\n\r\nPMID: 26765342;\r\n5 patients form 4 unrelated families (3 PTVs + 1 exon del). qPCR of total RNA demonstrated significantly reduced ADAMTS2 expression and LoF was further supported by functional assays using dermal fibroblasts. \r\nAuthors noted that Family 1 and Patient 5 are clinically milder and hypothesised that their C-term variants may lead to some transcripts escaping NMD, producing a truncated yet partially functional protein.\r\nFigure 2 provides an additional 6 previously reported variants (2 PTVs + 4 exon dels. \nSources: Literature",
"entity_name": "ADAMTS2",
"entity_type": "gene"
},
{
"created": "2020-07-01T11:13:50.397166+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.35",
"user_name": "Elena Savva",
"item_type": "entity",
"text": "gene: CRYAB was added\ngene: CRYAB was added to Limb Girdle Muscular Dystrophy. Sources: Expert list\nMode of inheritance for gene: CRYAB was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal\nPublications for gene: CRYAB were set to PMID: 21337604; 32420686\nPhenotypes for gene: CRYAB were set to Myopathy, myofibrillar, 2 608810; Myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related 613869\nReview for gene: CRYAB was set to AMBER\nAdded comment: PMID: 21337604 - 8 children with the same homozygous founder mutation and infantile onset muscular dystrophy. Truncal muscles reported to be more affected than limb muscles, phenotype was recapitulated in mouse models.\r\n\r\nPMID: 32420686 - monozygotic twin boys with a heterozygous PTC mutation. Patients showed congenital hypotonia, slightly elevated CK levels. Focal signs of muscle degeneration were observed, no particular mention of the location of muscle weakness. \nSources: Expert list",
"entity_name": "CRYAB",
"entity_type": "gene"
},
{
"created": "2020-07-01T10:52:36.912211+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.35",
"user_name": "Elena Savva",
"item_type": "entity",
"text": "gene: DES was added\ngene: DES was added to Limb Girdle Muscular Dystrophy. Sources: Expert list\nMode of inheritance for gene: DES was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal\nPublications for gene: DES were set to PMID: 20718792\nPhenotypes for gene: DES were set to Myopathy, myofibrillar, 1 601419\nReview for gene: DES was set to AMBER\nAdded comment: PMID: 20718792: large review of >100 patients. >70% had myopathy or muscle weakness, 67% presented with both distal and proximal muscle weakness.\r\nAuthors note myopathy generally begins with distal limbs, progressing later in life to proximal limb involvement. \nSources: Expert list",
"entity_name": "DES",
"entity_type": "gene"
},
{
"created": "2020-07-01T10:44:53.109228+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.35",
"user_name": "Crystle Lee",
"item_type": "entity",
"text": "gene: LPIN1 was added\ngene: LPIN1 was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review\nMode of inheritance for gene: LPIN1 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: LPIN1 were set to 28649549; 18817903; 32410653\nPhenotypes for gene: LPIN1 were set to Myoglobinuria, acute recurrent, autosomal recessive (MIM#268200)\nReview for gene: LPIN1 was set to AMBER\nAdded comment: Biallelic variants reported in>5 families. Rhabdomyolysis is a significant feature. Patients present with muscle weakness and elevated CK. Added as a differential diagnosis to LGMD (PanelApp UK) \nSources: Expert Review",
"entity_name": "LPIN1",
"entity_type": "gene"
},
{
"created": "2020-07-01T10:21:53.796662+10:00",
"panel_name": "Aortopathy_Connective Tissue Disorders",
"panel_id": 44,
"panel_version": "0.96",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "gene: ACVR1 was added\ngene: ACVR1 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature\nMode of inheritance for gene: ACVR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: ACVR1 were set to PMID: 30071989; 19085907; 26776312; 18684712; 23572558; 20463014\nPhenotypes for gene: ACVR1 were set to Fibrodysplasia ossificans progressiva (MIM# 135100)\nReview for gene: ACVR1 was set to AMBER\nAdded comment: Fibrodysplasia ossificans progressiva is a rare autosomal dominant disease with complete penetrance involving progressive ossification of skeletal muscle, fascia, tendons, and ligaments. \r\n\r\nPMID: 19085907; 112 FOP (classic and atypical) cases (104 sporadic and 8 families) with R206H has the recurrent variant and a greater clinical variability seen in non-R206H patients (PMID: 26776312)\r\n\r\nPMID: 18684712, 23572558, 20463014; functional studies demonstrating GoF\r\n\r\nPMID: 30071989; not a HTAAD gene by Clingen working group \nSources: Literature",
"entity_name": "ACVR1",
"entity_type": "gene"
},
{
"created": "2020-07-01T10:17:53.783655+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.35",
"user_name": "Crystle Lee",
"item_type": "entity",
"text": "gene: MYH7 was added\ngene: MYH7 was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review\nMode of inheritance for gene: MYH7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: MYH7 were set to 27387980; 20733148\nPhenotypes for gene: MYH7 were set to Laing distal myopathy (MIM#160500); Scapuloperoneal syndrome, myopathic type (MIM#181430)\nMode of pathogenicity for gene: MYH7 was set to Other\nReview for gene: MYH7 was set to AMBER\nAdded comment: Associated with a spectrum of skeletal myopathies which includes a scapuloperoneal or limb-girdle muscle form. \nSources: Expert Review",
"entity_name": "MYH7",
"entity_type": "gene"
},
{
"created": "2020-07-01T09:54:21.265871+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.35",
"user_name": "Crystle Lee",
"item_type": "entity",
"text": "gene: MYOT was added\ngene: MYOT was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review\nMode of inheritance for gene: MYOT was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: MYOT were set to 30055862; 21336781; 15947064\nPhenotypes for gene: MYOT were set to Myopathy, myofibrillar, 3\t(MIM#609200)\nReview for gene: MYOT was set to AMBER\nAdded comment: Associated phenotype was previously known as LGMD1/LGMD1A (OMIM; PMID: 30055862). Phenotypic overlap. \r\n\r\nPMID: 21336781: Reported a severe case of LGMD. Patient presented with late onset progressive proximal muscle weakness. CK was slightly elevated. Authors concluded that gene is a rare cause of adult onset LGMD. Variant present in gnomAD (12 hets). \r\n\r\nPMID: 15947064: 5 variants reported in 13 patients (including 3 families). Late onset, EMG showed myopathic changes in most patients. Highest MAF (10 hets in gnomAD; Ser60Phe). 9/13 did not show elevated CK levels. \nSources: Expert Review",
"entity_name": "MYOT",
"entity_type": "gene"
},
{
"created": "2020-07-01T09:50:41.759521+10:00",
"panel_name": "Aortopathy_Connective Tissue Disorders",
"panel_id": 44,
"panel_version": "0.96",
"user_name": "Paul De Fazio",
"item_type": "entity",
"text": "edited their review of gene: ZNF469: Changed phenotypes: Brittle cornea syndrome 1 MIM# 229200",
"entity_name": "ZNF469",
"entity_type": "gene"
},
{
"created": "2020-07-01T09:35:50.005736+10:00",
"panel_name": "Aortopathy_Connective Tissue Disorders",
"panel_id": 44,
"panel_version": "0.96",
"user_name": "Paul De Fazio",
"item_type": "entity",
"text": "gene: ZNF469 was added\ngene: ZNF469 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature\nMode of inheritance for gene: ZNF469 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: ZNF469 were set to 28306229; 28306225\nPhenotypes for gene: ZNF469 were set to Brittle cornea syndrome 1\nReview for gene: ZNF469 was set to GREEN\ngene: ZNF469 was marked as current diagnostic\nAdded comment: Association with brittle cornea syndrome (BCS) is well-established. 32 patients with variants in ZNF469 and BCS are reviewed in PMID: 28306225.\r\n\r\nBCS is classified as a form of Ehlers-Danlos syndrome (PMID: 28306229). \nSources: Literature",
"entity_name": "ZNF469",
"entity_type": "gene"
},
{
"created": "2020-07-01T09:35:31.411832+10:00",
"panel_name": "Aortopathy_Connective Tissue Disorders",
"panel_id": 44,
"panel_version": "0.96",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "gene: ABCC6 was added\ngene: ABCC6 was added to Aortopathy_Connective Tissue Disorders. Sources: Literature\nMode of inheritance for gene: ABCC6 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: ABCC6 were set to PMID: 30071989; 11536079\nPhenotypes for gene: ABCC6 were set to Pseudoxanthoma elasticum (MIM# 264800)\nReview for gene: ABCC6 was set to AMBER\nAdded comment: PMID: 30071989; not a gene for Heritable Thoracic Aortic Aneurysm and Dissection by Clingen Working Group\r\n\r\nPMID: 11536079; a cohort of 122 PXE patients were sequenced and 36 different variants were reported \nSources: Literature",
"entity_name": "ABCC6",
"entity_type": "gene"
},
{
"created": "2020-07-01T08:59:26.752745+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.35",
"user_name": "Crystle Lee",
"item_type": "entity",
"text": "gene: ORAI1 was added\ngene: ORAI1 was added to Limb Girdle Muscular Dystrophy. Sources: Expert Review\nMode of inheritance for gene: ORAI1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: ORAI1 were set to 31448844\nPhenotypes for gene: ORAI1 were set to Myopathy, tubular aggregate, 2 (MIM#615883)\nReview for gene: ORAI1 was set to AMBER\nAdded comment: OMIM notes both proximal and diffuse muscle weakness. There is some phenotypic overlap.\r\n\r\nPMID 31448844 (comprehensive review, summarises all published cases, references functional evidence): - Dominant ORAI1 missense variants via a GOF mechanism cause a slowly progressive myopathy (tubular aggregate myopathy/TAM) \nSources: Expert Review",
"entity_name": "ORAI1",
"entity_type": "gene"
},
{
"created": "2020-07-01T02:06:44.098709+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.3185",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "changed review comment from: PMID: 32202298 - Woldegebriel et al - report a further two families, one in the Netherlands and one in Estonia, with probands with compound heterozygous variants in MCM3AP and a peripheral neuropathy with or without impaired intellectual development (MIM 618124) phenotype. The child from the Netherlands presented with severe hypotonia and intellectual disability. The two siblings from the Estonian family had severe generalized epilepsy and mild spastic diplegia. Functional studies using skin fibroblasts from these and other affected patients showed that disease variants result in depletion of GANP (encoded by MCM3AP) except when they alter critical residues in the Sac3 mRNA binding domain. GANP depletion was associated with more severe phenotypes compared with the Sac3 variants.; to: PMID: 32202298 - Woldegebriel et al 2020 - report a further two families, one in the Netherlands and one in Estonia, with probands with compound heterozygous variants in MCM3AP and a peripheral neuropathy with or without impaired intellectual development (MIM 618124) phenotype. The child from the Netherlands presented with severe hypotonia and intellectual disability. The two siblings from the Estonian family had severe generalized epilepsy and mild spastic diplegia. Functional studies using skin fibroblasts from these and other affected patients showed that disease variants result in depletion of GANP (encoded by MCM3AP) except when they alter critical residues in the Sac3 mRNA binding domain. GANP depletion was associated with more severe phenotypes compared with the Sac3 variants.",
"entity_name": "MCM3AP",
"entity_type": "gene"
},
{
"created": "2020-07-01T02:01:46.662312+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.3185",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "reviewed gene: MCM3AP: Rating: ; Mode of pathogenicity: None; Publications: 32202298; Phenotypes: peripheral neuropathy with or without impaired intellectual development MIM#618124; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "MCM3AP",
"entity_type": "gene"
},
{
"created": "2020-07-01T01:13:09.634128+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.3185",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "gene: SP6 was added\ngene: SP6 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: SP6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: SP6 were set to 32167558; 18156176; 18297738; 22676574\nPhenotypes for gene: SP6 were set to hypoplastic amelogenesis imperfecta\nReview for gene: SP6 was set to AMBER\nAdded comment: PMID: 32167558 - Smith et al 2020 - report a 2 bp variant c.817_818GC>AA in SP6 in a Caucasian family with autosomal dominant hypoplastic AI which results in a missense change. Report that mice and rat knockouts also show a dental phenotype (PMID: 18156176, 18297738, 22676574 ) \nSources: Literature",
"entity_name": "SP6",
"entity_type": "gene"
},
{
"created": "2020-07-01T01:04:50.131393+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.3185",
"user_name": "Eleanor Williams",
"item_type": "entity",
"text": "reviewed gene: TBX5: Rating: GREEN; Mode of pathogenicity: None; Publications: 31373354; Phenotypes: Holt-Oram syndrome; Mode of inheritance: None",
"entity_name": "TBX5",
"entity_type": "gene"
},
{
"created": "2020-06-30T18:41:51.621155+10:00",
"panel_name": "Eye Anterior Segment Abnormalities",
"panel_id": 43,
"panel_version": "0.8",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: PAX6 as ready",
"entity_name": "PAX6",
"entity_type": "gene"
},
{
"created": "2020-06-30T18:41:51.611564+10:00",
"panel_name": "Eye Anterior Segment Abnormalities",
"panel_id": 43,
"panel_version": "0.8",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: pax6 has been classified as Green List (High Evidence).",
"entity_name": "PAX6",
"entity_type": "gene"
},
{
"created": "2020-06-30T18:41:47.396660+10:00",
"panel_name": "Eye Anterior Segment Abnormalities",
"panel_id": 43,
"panel_version": "0.8",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: PAX6 were changed from to Aniridia MIM# 106210; Anterior segment dysgenesis 5, multiple subtypes MIM# 6042293; Cataract with late-onset corneal dystrophy MIM# 106210; Foveal hypoplasia 1 MIM# 136520; Keratitis MIM# 148190; Optic nerve hypoplasia MIM# 165550",
"entity_name": "PAX6",
"entity_type": "gene"
},
{
"created": "2020-06-30T18:41:16.053031+10:00",
"panel_name": "Eye Anterior Segment Abnormalities",
"panel_id": 43,
"panel_version": "0.7",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: PAX6 were set to ",
"entity_name": "PAX6",
"entity_type": "gene"
},
{
"created": "2020-06-30T18:40:48.509948+10:00",
"panel_name": "Eye Anterior Segment Abnormalities",
"panel_id": 43,
"panel_version": "0.6",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: PAX6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "PAX6",
"entity_type": "gene"
},
{
"created": "2020-06-30T18:39:43.077295+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.3185",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: MYH8 as ready",
"entity_name": "MYH8",
"entity_type": "gene"
},
{
"created": "2020-06-30T18:39:43.069333+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.3185",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Added comment: Comment when marking as ready: Recurrent variant p.R674Q has occurred de novo in at least some families.",
"entity_name": "MYH8",
"entity_type": "gene"
},
{
"created": "2020-06-30T18:39:43.019478+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.3185",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: myh8 has been classified as Green List (High Evidence).",
"entity_name": "MYH8",
"entity_type": "gene"
},
{
"created": "2020-06-30T18:38:03.437200+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.3185",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: MYH8 were changed from to Trismus-pseudocamptodactyly syndrome MIM# 158300; Carney complex variant MIM# 608837",
"entity_name": "MYH8",
"entity_type": "gene"
},
{
"created": "2020-06-30T18:37:36.255322+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.3184",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: MYH8 were set to ",
"entity_name": "MYH8",
"entity_type": "gene"
},
{
"created": "2020-06-30T18:37:16.061096+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.3183",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: MYH8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "MYH8",
"entity_type": "gene"
},
{
"created": "2020-06-30T16:58:32.657014+10:00",
"panel_name": "Cutis Laxa",
"panel_id": 3129,
"panel_version": "0.5",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Marked gene: ATP6V1A as ready",
"entity_name": "ATP6V1A",
"entity_type": "gene"
},
{
"created": "2020-06-30T16:58:32.647046+10:00",
"panel_name": "Cutis Laxa",
"panel_id": 3129,
"panel_version": "0.5",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Gene: atp6v1a has been classified as Green List (High Evidence).",
"entity_name": "ATP6V1A",
"entity_type": "gene"
},
{
"created": "2020-06-30T16:58:29.501293+10:00",
"panel_name": "Cutis Laxa",
"panel_id": 3129,
"panel_version": "0.5",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Classified gene: ATP6V1A as Green List (high evidence)",
"entity_name": "ATP6V1A",
"entity_type": "gene"
},
{
"created": "2020-06-30T16:58:29.490995+10:00",
"panel_name": "Cutis Laxa",
"panel_id": 3129,
"panel_version": "0.5",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Gene: atp6v1a has been classified as Green List (High Evidence).",
"entity_name": "ATP6V1A",
"entity_type": "gene"
},
{
"created": "2020-06-30T16:58:20.496925+10:00",
"panel_name": "Cutis Laxa",
"panel_id": 3129,
"panel_version": "0.4",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "gene: ATP6V1A was added\ngene: ATP6V1A was added to Cutis Laxa. Sources: Literature\nMode of inheritance for gene: ATP6V1A was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: ATP6V1A were set to 28065471\nPhenotypes for gene: ATP6V1A were set to Cutis laxa, autosomal recessive, type IID MIM#617403\nReview for gene: ATP6V1A was set to GREEN\nAdded comment: 3 unrelated consanguineous families homozygous for 2 different missense variants (G72D, R338C), with supportive molecular analyses of patient cells. \nSources: Literature",
"entity_name": "ATP6V1A",
"entity_type": "gene"
},
{
"created": "2020-06-30T16:39:45.692324+10:00",
"panel_name": "Cutis Laxa",
"panel_id": 3129,
"panel_version": "0.3",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Marked gene: ATP6V1E1 as ready",
"entity_name": "ATP6V1E1",
"entity_type": "gene"
},
{
"created": "2020-06-30T16:39:45.682723+10:00",
"panel_name": "Cutis Laxa",
"panel_id": 3129,
"panel_version": "0.3",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Gene: atp6v1e1 has been classified as Green List (High Evidence).",
"entity_name": "ATP6V1E1",
"entity_type": "gene"
},
{
"created": "2020-06-30T16:39:42.885909+10:00",
"panel_name": "Cutis Laxa",
"panel_id": 3129,
"panel_version": "0.3",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Classified gene: ATP6V1E1 as Green List (high evidence)",
"entity_name": "ATP6V1E1",
"entity_type": "gene"
},
{
"created": "2020-06-30T16:39:42.872763+10:00",
"panel_name": "Cutis Laxa",
"panel_id": 3129,
"panel_version": "0.3",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Gene: atp6v1e1 has been classified as Green List (High Evidence).",
"entity_name": "ATP6V1E1",
"entity_type": "gene"
},
{
"created": "2020-06-30T16:39:29.576501+10:00",
"panel_name": "Cutis Laxa",
"panel_id": 3129,
"panel_version": "0.2",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "gene: ATP6V1E1 was added\ngene: ATP6V1E1 was added to Cutis Laxa. Sources: Expert list\nMode of inheritance for gene: ATP6V1E1 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: ATP6V1E1 were set to 28065471; 27023906\nPhenotypes for gene: ATP6V1E1 were set to Cutis laxa, autosomal recessive, type IIC MIM#617402\nReview for gene: ATP6V1E1 was set to GREEN\nAdded comment: 3 unrelated consanguineous families homozygous for 2 different missense variants (L128P, R212W) with paediatric onset cutis laxa. Molecular anlayses of patient tissues was supportive. \nSources: Expert list",
"entity_name": "ATP6V1E1",
"entity_type": "gene"
},
{
"created": "2020-06-30T12:49:56.479860+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.3182",
"user_name": "Teresa Zhao",
"item_type": "entity",
"text": "reviewed gene: MYH8: Rating: GREEN; Mode of pathogenicity: Other; Publications: 28377322, 18049072, 17041932; Phenotypes: Trismus-pseudocamptodactyly syndrome MIM# 158300, Carney complex variant MIM# 608837; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown",
"entity_name": "MYH8",
"entity_type": "gene"
},
{
"created": "2020-06-30T11:58:02.857383+10:00",
"panel_name": "Eye Anterior Segment Abnormalities",
"panel_id": 43,
"panel_version": "0.5",
"user_name": "Teresa Zhao",
"item_type": "entity",
"text": "changed review comment from: Loss of function is a well established mechanism. \r\n\r\nThis protein consists of paried domain (PD), which consists of N-terminal sub-domain (PAI domain), homeodomain (HD) and C-terminal sub-domain (RED domain) (PMID: 26899008).\r\n\r\nExon 5a of 14 additional aa is inserted into N-terminal sub-domain abolishes the DNA-binding ability of C-terminal sub-domain and functions as a molecular switch that selects and spedifies target genes (PMID: 20132240).\r\n\r\nPAX6 has two isoforms, a and b, they cooperatively act in the development of both the posterior and anterior segment of the eye by regulating different gens (PMID: 26899008).\r\nisoform a: induces KRT3 expression.\r\nisoform b: indluced KRT12 expression when combined with KLF4 and OCT4.; to: Loss of function is a well established mechanism. \r\n\r\nThis protein consists of paried domain (PD), which consists of N-terminal sub-domain (PAI domain), homeodomain (HD) and C-terminal sub-domain (RED domain) (PMID: 26899008).\r\n\r\nExon 5a of 14 additional aa is inserted into N-terminal sub-domain abolishes the DNA-binding ability of C-terminal sub-domain and functions as a molecular switch that selects and spedifies target genes (PMID: 20132240).\r\n\r\nPAX6 has two isoforms, a and b, they cooperatively act in the development of both the posterior and anterior segment of the eye by regulating different genes (PMID: 26899008).\r\nisoform a: induces KRT3 expression.\r\nisoform b: indluced KRT12 expression when combined with KLF4 and OCT4.",
"entity_name": "PAX6",
"entity_type": "gene"
},
{
"created": "2020-06-30T11:57:29.686993+10:00",
"panel_name": "Eye Anterior Segment Abnormalities",
"panel_id": 43,
"panel_version": "0.5",
"user_name": "Teresa Zhao",
"item_type": "entity",
"text": "reviewed gene: PAX6: Rating: GREEN; Mode of pathogenicity: None; Publications: 27081561, 20132240, 26899008; Phenotypes: ?Coloboma of optic nerve MIM# 120430, ?Coloboma, ocular MIM# 120200, ?Morning glory disc anomaly MIM# 120430, Aniridia MIM# 106210, Anterior segment dysgenesis 5, multiple subtypes MIM# 6042293, Cataract with late-onset corneal dystrophy MIM# 106210, Foveal hypoplasia 1 MIM# 136520, Keratitis MIM# 148190, Optic nerve hypoplasia MIM# 165550; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown",
"entity_name": "PAX6",
"entity_type": "gene"
},
{
"created": "2020-06-30T03:23:07.945712+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.3182",
"user_name": "sarah leigh",
"item_type": "entity",
"text": "reviewed gene: SKIV2L: Rating: AMBER; Mode of pathogenicity: None; Publications: 29334452; Phenotypes: Intellectual disability; Mode of inheritance: None",
"entity_name": "SKIV2L",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:51:09.077238+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.35",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: PFKM as ready",
"entity_name": "PFKM",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:51:09.067141+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.35",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Added comment: Comment when marking as ready: Some phenotypic overlap.",
"entity_name": "PFKM",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:51:09.025104+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.35",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: pfkm has been classified as Amber List (Moderate Evidence).",
"entity_name": "PFKM",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:50:56.399819+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.35",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: PFKM as Amber List (moderate evidence)",
"entity_name": "PFKM",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:50:56.390677+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.35",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: pfkm has been classified as Amber List (Moderate Evidence).",
"entity_name": "PFKM",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:50:36.779120+10:00",
"panel_name": "Glycogen Storage Diseases",
"panel_id": 106,
"panel_version": "0.11",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: PFKM as ready",
"entity_name": "PFKM",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:50:36.769002+10:00",
"panel_name": "Glycogen Storage Diseases",
"panel_id": 106,
"panel_version": "0.11",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: pfkm has been classified as Green List (High Evidence).",
"entity_name": "PFKM",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:50:33.213503+10:00",
"panel_name": "Glycogen Storage Diseases",
"panel_id": 106,
"panel_version": "0.11",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: PFKM were changed from to Glycogen storage disease VII (MIM#232800)",
"entity_name": "PFKM",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:50:00.929614+10:00",
"panel_name": "Glycogen Storage Diseases",
"panel_id": 106,
"panel_version": "0.10",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: PFKM were set to ",
"entity_name": "PFKM",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:48:59.711087+10:00",
"panel_name": "Glycogen Storage Diseases",
"panel_id": 106,
"panel_version": "0.9",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: PFKM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "PFKM",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:45:48.315452+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.34",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: POMK as ready",
"entity_name": "POMK",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:45:48.301612+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.34",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: pomk has been classified as Amber List (Moderate Evidence).",
"entity_name": "POMK",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:45:43.146629+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.34",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: POMK were set to ",
"entity_name": "POMK",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:45:34.891525+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.33",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: POMK as Amber List (moderate evidence)",
"entity_name": "POMK",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:45:34.877455+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.33",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: pomk has been classified as Amber List (Moderate Evidence).",
"entity_name": "POMK",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:44:40.386055+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.32",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: CAV3 as ready",
"entity_name": "CAV3",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:44:40.379715+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.32",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Added comment: Comment when marking as ready: Phenotypic overlap.",
"entity_name": "CAV3",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:44:40.334865+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.32",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: cav3 has been classified as Amber List (Moderate Evidence).",
"entity_name": "CAV3",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:44:30.569101+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.32",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: CAV3 as Amber List (moderate evidence)",
"entity_name": "CAV3",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:44:30.543266+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.32",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: cav3 has been classified as Amber List (Moderate Evidence).",
"entity_name": "CAV3",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:42:55.490267+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.31",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: PYGM as ready",
"entity_name": "PYGM",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:42:55.483912+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.31",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Added comment: Comment when marking as ready: Phenotypic overlap.",
"entity_name": "PYGM",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:42:55.438297+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.31",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: pygm has been classified as Amber List (Moderate Evidence).",
"entity_name": "PYGM",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:42:45.851338+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.31",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: PYGM as Amber List (moderate evidence)",
"entity_name": "PYGM",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:42:45.839204+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.31",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: pygm has been classified as Amber List (Moderate Evidence).",
"entity_name": "PYGM",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:42:08.240525+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.30",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: CASQ1 as ready",
"entity_name": "CASQ1",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:42:08.235885+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.30",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Added comment: Comment when marking as ready: Founder variant, but large number of affected individuals reported. Italian, rather than rare, isolated ethnicity.",
"entity_name": "CASQ1",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:42:08.203663+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.30",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: casq1 has been classified as Green List (High Evidence).",
"entity_name": "CASQ1",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:41:25.060278+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.30",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: CASQ1 as Green List (high evidence)",
"entity_name": "CASQ1",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:41:25.046992+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.30",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: casq1 has been classified as Green List (High Evidence).",
"entity_name": "CASQ1",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:41:17.720530+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.29",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Tag founder tag was added to gene: CASQ1.",
"entity_name": "CASQ1",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:36:41.247047+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.3182",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: CACNB1 as ready",
"entity_name": "CACNB1",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:36:41.234884+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.3182",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: cacnb1 has been classified as Red List (Low Evidence).",
"entity_name": "CACNB1",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:36:24.432361+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.3182",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "gene: CACNB1 was added\ngene: CACNB1 was added to Mendeliome. Sources: Expert list\nMode of inheritance for gene: CACNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: CACNB1 were set to 27832566; 8943043; 29212769\nPhenotypes for gene: CACNB1 were set to Malignant hyperthermia susceptibility\nAdded comment: A single heterozygous case with a positive IVCT muscle biopsy has been reported with p.Val156Ala. The European non-Finnish allele frequency in gnomAD v2.1 is 0.001146 (148/129,118 alleles), which is higher than the expected population frequency for dominantly inherited malignant hyperthermia (0.1%). Additionally, functional assays of this variant, suggest it would only significantly affect function in the homozygous state (suggesting a recessive condition). \nSources: Expert list",
"entity_name": "CACNB1",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:32:14.340304+10:00",
"panel_name": "Skeletal Muscle Channelopathies",
"panel_id": 302,
"panel_version": "0.6",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: CACNB1 as ready",
"entity_name": "CACNB1",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:32:14.330360+10:00",
"panel_name": "Skeletal Muscle Channelopathies",
"panel_id": 302,
"panel_version": "0.6",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: cacnb1 has been classified as Red List (Low Evidence).",
"entity_name": "CACNB1",
"entity_type": "gene"
},
{
"created": "2020-06-29T20:29:45.004331+10:00",
"panel_name": "Limb Girdle Muscular Dystrophy",
"panel_id": 3071,
"panel_version": "0.29",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: PYROXD1 were set to 30515627",
"entity_name": "PYROXD1",
"entity_type": "gene"
}
]
}