{"count":221304,"next":"https://panelapp-aus.org/api/v1/activities/?format=json&page=651","previous":"https://panelapp-aus.org/api/v1/activities/?format=json&page=649","results":[{"created":"2022-12-30T08:52:36.758279+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1749","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: prkar1a has been classified as Green List (High Evidence).","entity_name":"PRKAR1A","entity_type":"gene"},{"created":"2022-12-30T08:52:25.028776+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1748","user_name":"Zornitza Stark","item_type":"entity","text":"Tag for review tag was added to gene: PRKAR1A.\nTag cancer tag was added to gene: PRKAR1A.\nTag treatable tag was added to gene: PRKAR1A.","entity_name":"PRKAR1A","entity_type":"gene"},{"created":"2022-12-30T08:52:08.375273+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1748","user_name":"Zornitza Stark","item_type":"entity","text":"Deleted their comment","entity_name":"PRKAR1A","entity_type":"gene"},{"created":"2022-12-30T08:51:59.948535+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1748","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: PRKAR1A: Added comment: Rated as 'strong actionability' in paediatric patients by ClinGen, principally due to benefit from early detection of cardiac myxomas through surveillance.\r\n\r\nCNC is associated with skin pigmentary abnormalities, myxomas, endocrine tumors or overactivity, and schwannomas. \r\n\r\nLentigines are the most common presenting feature of CNC and may be present at birth. Typically, they increase in number at puberty, fade after the fourth decade, but may still be evident in the eighth decade. Cutaneous myxomas appear between birth and the fourth decade. Cardiac myxomas may occur at a young age. Breast myxomas occur in females after puberty. Males and females may develop nipple myxomas at any age. In a minority of individuals, PPNAD presents in the first two to three years; in the majority, it presents in the second or third decade. LCCSCT often present in the first decade. Signs and symptoms of CNC may be present at birth, but the median age of diagnosis is 20 years. Most patients with CNC present with a mild increase in GH. However, clinically evident acromegaly is a relatively frequent manifestation of CNC, occurring in approximately 10% of adults at the time of presentation. Most individuals with CNC have a normal life span. However, because some die at an early age, the average life expectancy for individuals with CNC is 50 years. Causes of death include complications of cardiac myxoma (myxoma emboli, cardiomyopathy, cardiac arrhythmia, and surgical intervention), metastatic or intracranial PMS, thyroid carcinoma, and metastatic pancreatic and testicular tumors.\r\n\r\nThe only preventive measure in an asymptomatic individual is surgical removal of a heart tumor (cardiac myxoma) prior to the development of heart dysfunction, stroke, or other embolism. Cardiac myxomas should be diagnosed early through regular screening.\r\n\r\nDevelopment of metabolic abnormalities from Cushing syndrome or arthropathy and other complications from acromegaly may be prevented by medical or surgical treatment of the respective endocrine manifestations.\r\n\r\nThe overall penetrance of CNC in those with a PRKAR1A pathogenic variant is greater than 95% by age 50 years. 30-60% have cardiac myxomas.; Changed rating: GREEN; Changed phenotypes: Carney complex, type 1, MIM# 160980","entity_name":"PRKAR1A","entity_type":"gene"},{"created":"2022-12-29T20:11:47.910143+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1748","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: RPS10 as ready","entity_name":"RPS10","entity_type":"gene"},{"created":"2022-12-29T20:11:47.898431+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1748","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: rps10 has been classified as Green List (High Evidence).","entity_name":"RPS10","entity_type":"gene"},{"created":"2022-12-29T20:11:44.397496+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1748","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: RPS10 were changed from Diamond-Blackfan anaemia 9, MIM#\t613308; Diamond-Blackfan anemia to Diamond-Blackfan anaemia 9, MIM#\t613308","entity_name":"RPS10","entity_type":"gene"},{"created":"2022-12-29T20:11:31.076750+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1747","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: RPS10 as Green List (high evidence)","entity_name":"RPS10","entity_type":"gene"},{"created":"2022-12-29T20:11:31.064696+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1747","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: rps10 has been classified as Green List (High Evidence).","entity_name":"RPS10","entity_type":"gene"},{"created":"2022-12-29T20:11:21.820829+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1746","user_name":"Zornitza Stark","item_type":"entity","text":"Tag treatable tag was added to gene: RPS10.\nTag haematological tag was added to gene: RPS10.","entity_name":"RPS10","entity_type":"gene"},{"created":"2022-12-29T20:11:11.051511+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1746","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: RPS10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diamond-Blackfan anaemia 9, MIM# 613308; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"RPS10","entity_type":"gene"},{"created":"2022-12-29T20:05:22.394691+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1746","user_name":"Zornitza Stark","item_type":"entity","text":"Tag treatable tag was added to gene: MEN1.","entity_name":"MEN1","entity_type":"gene"},{"created":"2022-12-29T20:05:09.545258+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1746","user_name":"Zornitza Stark","item_type":"entity","text":"changed review comment from: For review re age of onset: surveillance starts age 5, disease onset generally later.; to: For review re age of onset: surveillance starts age 5, disease onset generally later.\r\n\r\nRated as 'strong actionability' in paediatric patients by ClinGen.\r\n\r\nParathyroid tumors, which cause PHPT, are the most common feature and the first clinical manifestation in 90% of individuals with MEN1 with onset typically between ages 20 and 25 years. Almost all (95-100%) individuals with MEN1 can expect to have PHPT by age 50 years. However, MEN1 affects all age groups, with a reported age range of 5 to 81 years; 17% of MEN1 tumors are diagnosed under age 21. Untreated patients with MEN1 have a decreased life expectancy with a 50% probability of death by age 50. The cause of death in 50-70% of cases is due to a malignant tumor process or sequelae of the disease, with malignancies accounting for 30% of all deaths.","entity_name":"MEN1","entity_type":"gene"},{"created":"2022-12-29T20:03:16.297296+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1746","user_name":"Zornitza Stark","item_type":"entity","text":"Tag for review tag was added to gene: MEN1.\nTag cancer tag was added to gene: MEN1.","entity_name":"MEN1","entity_type":"gene"},{"created":"2022-12-29T20:02:27.539828+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1746","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: SCN5A as ready","entity_name":"SCN5A","entity_type":"gene"},{"created":"2022-12-29T20:02:27.527561+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1746","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: scn5a has been classified as Amber List (Moderate Evidence).","entity_name":"SCN5A","entity_type":"gene"},{"created":"2022-12-29T20:02:23.346573+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1746","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: SCN5A were changed from Sick sinus syndrome 1, MIM# 608567; Ventricular fibrillation, familial, 1, MIM# 603829; Brugada syndrome; Brugada syndrome 1, MIM# 601144; Long QT syndrome 3 (MIM#603830); Long QT syndrome; Heart block, progressive, type IA, MIM# 113900 to Long QT syndrome 3 (MIM#603830); Brugada syndrome 1, MIM# 601144","entity_name":"SCN5A","entity_type":"gene"},{"created":"2022-12-29T20:02:09.372750+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1745","user_name":"Zornitza Stark","item_type":"entity","text":"Tag for review tag was added to gene: SCN5A.\nTag cardiac tag was added to gene: SCN5A.\nTag treatable tag was added to gene: SCN5A.","entity_name":"SCN5A","entity_type":"gene"},{"created":"2022-12-29T20:01:56.589972+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1745","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: SCN5A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Long QT syndrome 3 (MIM#603830), Brugada syndrome 1, MIM# 601144; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"SCN5A","entity_type":"gene"},{"created":"2022-12-29T19:58:50.243241+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1745","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: SLC26A4 were changed from Pendred syndrome, MIM #274600 to Deafness, autosomal recessive 4, with enlarged vestibular aqueduct 600791; Pendred syndrome 274600","entity_name":"SLC26A4","entity_type":"gene"},{"created":"2022-12-29T19:58:38.063744+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1744","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: SLC26A4 as Green List (high evidence)","entity_name":"SLC26A4","entity_type":"gene"},{"created":"2022-12-29T19:58:38.049401+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1744","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: slc26a4 has been classified as Green List (High Evidence).","entity_name":"SLC26A4","entity_type":"gene"},{"created":"2022-12-29T19:58:28.764876+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1743","user_name":"Zornitza Stark","item_type":"entity","text":"Tag for review was removed from gene: SLC26A4.\nTag deafness tag was added to gene: SLC26A4.","entity_name":"SLC26A4","entity_type":"gene"},{"created":"2022-12-29T19:58:16.369499+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1743","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: SLC26A4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 4, with enlarged vestibular aqueduct 600791, Pendred syndrome 274600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"SLC26A4","entity_type":"gene"},{"created":"2022-12-29T19:49:25.374779+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1743","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: TGFB3 as ready","entity_name":"TGFB3","entity_type":"gene"},{"created":"2022-12-29T19:49:25.362284+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1743","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: tgfb3 has been classified as Green List (High Evidence).","entity_name":"TGFB3","entity_type":"gene"},{"created":"2022-12-29T19:49:17.801511+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1743","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: TGFB3 were changed from Arrhythmogenic right ventricular dysplasia to Loeys-Dietz syndrome 5 , MIM#615582","entity_name":"TGFB3","entity_type":"gene"},{"created":"2022-12-29T19:49:02.127842+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1742","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: TGFB3 as Green List (high evidence)","entity_name":"TGFB3","entity_type":"gene"},{"created":"2022-12-29T19:49:02.103326+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1742","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: tgfb3 has been classified as Green List (High Evidence).","entity_name":"TGFB3","entity_type":"gene"},{"created":"2022-12-29T19:48:52.226921+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1741","user_name":"Zornitza Stark","item_type":"entity","text":"Tag for review tag was added to gene: TGFB3.\nTag cardiac tag was added to gene: TGFB3.\nTag treatable tag was added to gene: TGFB3.","entity_name":"TGFB3","entity_type":"gene"},{"created":"2022-12-29T19:48:38.007555+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1741","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: TGFB3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Loeys-Dietz syndrome 5 , MIM#615582; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"TGFB3","entity_type":"gene"},{"created":"2022-12-29T19:47:21.760228+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1741","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: TGFB2 as ready","entity_name":"TGFB2","entity_type":"gene"},{"created":"2022-12-29T19:47:21.747201+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1741","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: tgfb2 has been classified as Green List (High Evidence).","entity_name":"TGFB2","entity_type":"gene"},{"created":"2022-12-29T19:47:14.493844+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1741","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: TGFB2 as Green List (high evidence)","entity_name":"TGFB2","entity_type":"gene"},{"created":"2022-12-29T19:47:14.479284+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1741","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: tgfb2 has been classified as Green List (High Evidence).","entity_name":"TGFB2","entity_type":"gene"},{"created":"2022-12-29T19:47:03.743792+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1740","user_name":"Zornitza Stark","item_type":"entity","text":"Tag for review tag was added to gene: TGFB2.\nTag cardiac tag was added to gene: TGFB2.\nTag treatable tag was added to gene: TGFB2.","entity_name":"TGFB2","entity_type":"gene"},{"created":"2022-12-29T19:46:48.457904+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1740","user_name":"Zornitza Stark","item_type":"entity","text":"gene: TGFB2 was added\ngene: TGFB2 was added to gNBS. Sources: ClinGen\nMode of inheritance for gene: TGFB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPhenotypes for gene: TGFB2 were set to Loeys-Dietz syndrome 4, MIM#\t614816\nReview for gene: TGFB2 was set to GREEN\nAdded comment: Rated as 'strong actionability' in paediatric patients by ClinGen.\r\n\r\nIndividuals with LDS are predisposed to widespread and aggressive arterial aneurysms which are the major source of morbidity and mortality. Aortic growth can be faster than 10mm per year. Aortic dissection has been observed in early childhood, and the mean age of death is 26 years. Other life-threatening manifestations include spontaneous rupture of the spleen, bowel, and uterine rupture during pregnancy.\r\n\r\nProphylactic surgical repair is typically recommended at an aortic diameter of ≥ 4.2 cm.\r\n\r\nBeta-blockers or other medications can be used to reduce hemodynamic stress.\r\n\r\nConsider Medicalert bracelet.\r\n\r\nUse of subacute bacterial endocarditis prophylaxis should be considered for individuals with connective tissue disorders and documented evidence of mitral and/or aortic regurgitation who are undergoing dental work or other procedures expected to contaminate the bloodstream with bacteria.\r\n\r\nBecause of a high risk of cervical spine instability, a flexion and extension x-ray of the cervical spine should be performed prior to intubation or any other procedure involving manipulation of the neck. \nSources: ClinGen","entity_name":"TGFB2","entity_type":"gene"},{"created":"2022-12-29T19:42:12.750647+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1739","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: TRDN as ready","entity_name":"TRDN","entity_type":"gene"},{"created":"2022-12-29T19:42:12.739360+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1739","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: trdn has been classified as Green List (High Evidence).","entity_name":"TRDN","entity_type":"gene"},{"created":"2022-12-29T19:41:57.139117+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1739","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: TRDN were changed from Catecholaminergic polymorphic ventricular tachycardia to Cardiac arrhythmia syndrome, with or without skeletal muscle weakness, MIM# 615441","entity_name":"TRDN","entity_type":"gene"},{"created":"2022-12-29T19:41:41.699936+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1738","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: TRDN as Green List (high evidence)","entity_name":"TRDN","entity_type":"gene"},{"created":"2022-12-29T19:41:41.684952+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1738","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: trdn has been classified as Green List (High Evidence).","entity_name":"TRDN","entity_type":"gene"},{"created":"2022-12-29T19:41:32.266614+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1737","user_name":"Zornitza Stark","item_type":"entity","text":"Tag for review tag was added to gene: TRDN.\nTag cardiac tag was added to gene: TRDN.\nTag treatable tag was added to gene: TRDN.","entity_name":"TRDN","entity_type":"gene"},{"created":"2022-12-29T19:41:14.311814+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1737","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: TRDN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiac arrhythmia syndrome, with or without skeletal muscle weakness, MIM# 615441; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"TRDN","entity_type":"gene"},{"created":"2022-12-29T19:39:58.320895+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1737","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: TECRL as ready","entity_name":"TECRL","entity_type":"gene"},{"created":"2022-12-29T19:39:58.302281+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1737","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: tecrl has been classified as Green List (High Evidence).","entity_name":"TECRL","entity_type":"gene"},{"created":"2022-12-29T19:39:52.665921+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1737","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: TECRL as Green List (high evidence)","entity_name":"TECRL","entity_type":"gene"},{"created":"2022-12-29T19:39:52.653391+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1737","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: tecrl has been classified as Green List (High Evidence).","entity_name":"TECRL","entity_type":"gene"},{"created":"2022-12-29T19:39:38.120869+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1736","user_name":"Zornitza Stark","item_type":"entity","text":"gene: TECRL was added\ngene: TECRL was added to gNBS. Sources: ClinGen\nfor review, cardiac, treatable tags were added to gene: TECRL.\nMode of inheritance for gene: TECRL was set to BIALLELIC, autosomal or pseudoautosomal\nPhenotypes for gene: TECRL were set to Ventricular tachycardia, catecholaminergic polymorphic, 3, MIM#\t614021\nReview for gene: TECRL was set to GREEN\nAdded comment: Rated as 'strong actionability' for paediatric patients by ClinGen.\r\n\r\nThe mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease.\r\n\r\nBeta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.\r\n\r\nIn patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.\r\n\r\nClinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.\r\n\r\nFor review: age of onset and penetrance. \nSources: ClinGen","entity_name":"TECRL","entity_type":"gene"},{"created":"2022-12-29T19:35:34.972007+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1735","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: CALM3 as ready","entity_name":"CALM3","entity_type":"gene"},{"created":"2022-12-29T19:35:34.959711+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1735","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: calm3 has been classified as Green List (High Evidence).","entity_name":"CALM3","entity_type":"gene"},{"created":"2022-12-29T19:35:27.280638+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1735","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: CALM3 as Green List (high evidence)","entity_name":"CALM3","entity_type":"gene"},{"created":"2022-12-29T19:35:27.264887+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1735","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: calm3 has been classified as Green List (High Evidence).","entity_name":"CALM3","entity_type":"gene"},{"created":"2022-12-29T19:35:14.222232+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1734","user_name":"Zornitza Stark","item_type":"entity","text":"gene: CALM3 was added\ngene: CALM3 was added to gNBS. Sources: ClinGen\nfor review, cardiac, treatable tags were added to gene: CALM3.\nMode of inheritance for gene: CALM3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPhenotypes for gene: CALM3 were set to Ventricular tachycardia, catecholaminergic polymorphic 6 , MIM#\t618782\nPenetrance for gene: CALM3 were set to Incomplete\nReview for gene: CALM3 was set to GREEN\nAdded comment: Rated as 'strong actionability' for paediatric patients by ClinGen.\r\n\r\nThe mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.\r\n\r\nIndividuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.\r\n\r\nBeta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.\r\n\r\nIn patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.\r\n\r\nClinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.\r\n\r\nFor review: age of onset and penetrance. \nSources: ClinGen","entity_name":"CALM3","entity_type":"gene"},{"created":"2022-12-29T19:33:44.216070+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1733","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: CALM2 as ready","entity_name":"CALM2","entity_type":"gene"},{"created":"2022-12-29T19:33:44.204553+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1733","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: calm2 has been classified as Green List (High Evidence).","entity_name":"CALM2","entity_type":"gene"},{"created":"2022-12-29T19:33:38.592155+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1733","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: CALM2 as Green List (high evidence)","entity_name":"CALM2","entity_type":"gene"},{"created":"2022-12-29T19:33:38.581092+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1733","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: calm2 has been classified as Green List (High Evidence).","entity_name":"CALM2","entity_type":"gene"},{"created":"2022-12-29T19:33:25.730958+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1732","user_name":"Zornitza Stark","item_type":"entity","text":"gene: CALM2 was added\ngene: CALM2 was added to gNBS. Sources: ClinGen\nfor review, cardiac, treatable tags were added to gene: CALM2.\nMode of inheritance for gene: CALM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPhenotypes for gene: CALM2 were set to Catecholaminergic polymorphic ventricular tachycardia MONDO:0017990\nReview for gene: CALM2 was set to GREEN\nAdded comment: Rated as 'strong actionability' for paediatric patients by ClinGen.\r\n\r\nThe mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.\r\n\r\nIndividuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.\r\n\r\nBeta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.\r\n\r\nIn patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.\r\n\r\nClinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.\r\n\r\nFor review: age of onset and penetrance. \nSources: ClinGen","entity_name":"CALM2","entity_type":"gene"},{"created":"2022-12-29T19:33:05.443258+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1731","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: CALM1 as ready","entity_name":"CALM1","entity_type":"gene"},{"created":"2022-12-29T19:33:05.431083+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1731","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: calm1 has been classified as Green List (High Evidence).","entity_name":"CALM1","entity_type":"gene"},{"created":"2022-12-29T19:31:28.733190+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1731","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: CALM1 as Green List (high evidence)","entity_name":"CALM1","entity_type":"gene"},{"created":"2022-12-29T19:31:28.719529+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1731","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: calm1 has been classified as Green List (High Evidence).","entity_name":"CALM1","entity_type":"gene"},{"created":"2022-12-29T19:31:15.153472+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1730","user_name":"Zornitza Stark","item_type":"entity","text":"gene: CALM1 was added\ngene: CALM1 was added to gNBS. Sources: ClinGen\nfor review, cardiac, treatable tags were added to gene: CALM1.\nMode of inheritance for gene: CALM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPhenotypes for gene: CALM1 were set to Ventricular tachycardia, catecholaminergic polymorphic, 4, MIM# 614916\nPenetrance for gene: CALM1 were set to Incomplete\nReview for gene: CALM1 was set to GREEN\nAdded comment: Rated as 'strong actionability' for paediatric patients by ClinGen.\r\n\r\nThe mean age of onset of symptoms (usually a syncopal episode) of CPVT is between age seven and twelve years; onset as late as the fourth decade of life has been reported. Nearly 60% of patients have at least one syncopal episode before age 40. If untreated, CPVT is highly lethal, as approximately 30% of genetically affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. In untreated patients, the 8-year fatal or near-fatal event rates of 25% have been reported. Sudden death may be the first manifestation of the disease. Instances of sudden infant death syndrome (SIDS) have been associated with pathogenic variants in RYR2.\r\n\r\nIndividuals with pathogenic variants in CALM1, CALM2 or CALM3 can have a severe phenotype, with earlier onset, QT prolongation, and a high predilection for cardiac arrest and sudden death.\r\n\r\nBeta-blockers lacking intrinsic sympathomimetic activity are recommended as a first-line therapy in all patients with a clinical diagnosis of CPVT, including those with documented spontaneous, stress-induced VAs. Guidelines differ in their recommendations about utilizing beta-blocker therapy in phenotype negative individuals. Treatment with beta blockers is associated with a reduction in adverse cardiac events. However, variability in outcome with beta-blocker therapy is due to multiple factors, including dosing and compliance. In a study of 101 patients with CPVT (22 diagnosed clinically and 79 diagnosed molecularly), 81 were administered beta-blockers (57 symptomatic and 24 asymptomatic individuals). Estimated 4- and 8-year cardiac event rates were 8% and 27%, respectively in patients taking beta-blockers, and 33% and 58% in those not taking beta blockers (log-rank p=0.01). Corresponding statistics for fatal events were 1% and 11% with beta-blockers vs. 18% and 25% without (log-rank p=0.05). Event rates in asymptomatic patients with a positive genotype were similar to other patients. In multivariate models, absence of beta-blockers was an independent predictor of cardiac events (hazard ratio [HR], 5.48; 95% CI, 1.8 to 16.7, p=0.003) and of fatal events (HR, 5.54; 95% CI, 1.2 to 26.1, p=0.03). Of the 37 asymptomatic patients with a positive genotype, 9 (24%) had cardiac events.\r\n\r\nIn patients with CPVT and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (e.g., beta blocker with flecainide), left cardiac sympathetic denervation, and/or an ICD is recommended.\r\n\r\nClinical penetrance ranges from 25 to 100%, with an average of 70 to 80%. Syncope appears to be the first symptom in more than half of the patients. When untreated, mortality from CPVT is high, reaching 30 to 50% by the age of 30 years.\r\n\r\nFor review: age of onset and penetrance. \nSources: ClinGen","entity_name":"CALM1","entity_type":"gene"},{"created":"2022-12-29T19:24:24.453820+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1729","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: RPE65 as ready","entity_name":"RPE65","entity_type":"gene"},{"created":"2022-12-29T19:24:24.441409+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1729","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: rpe65 has been classified as Green List (High Evidence).","entity_name":"RPE65","entity_type":"gene"},{"created":"2022-12-29T19:24:16.517376+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1729","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: RPE65 as Green List (high evidence)","entity_name":"RPE65","entity_type":"gene"},{"created":"2022-12-29T19:24:16.504484+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1729","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: rpe65 has been classified as Green List (High Evidence).","entity_name":"RPE65","entity_type":"gene"},{"created":"2022-12-29T19:24:01.896294+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1728","user_name":"Zornitza Stark","item_type":"entity","text":"gene: RPE65 was added\ngene: RPE65 was added to gNBS. Sources: ClinGen\nfor review, treatable, ophthalmological tags were added to gene: RPE65.\nMode of inheritance for gene: RPE65 was set to BIALLELIC, autosomal or pseudoautosomal\nPhenotypes for gene: RPE65 were set to Leber congenital amaurosis 2 MIM#204100; Retinitis pigmentosa 20 MIM#613794\nReview for gene: RPE65 was set to GREEN\nAdded comment: Assessed as 'strong actionability' in paediatric patients by ClinGen.\r\n\r\nBiallelic RPE65 mutation-associated retinal dystrophy is a form of IRD caused by biallelic pathogenic variants in RPE65; it presents as a spectrum of disease with variable age of onset and progression of vision loss. Common clinical findings across the spectrum include night blindness, progressive loss of visual fields and loss of central vision. \r\n\r\nIn LCA, night blindness often occurs from birth. Characteristically, these patients have residual cone-mediated vision in the first to third decades with progressive visual field loss until complete blindness is observed, most often in mid- to late-adulthood. A range of age of onset has been described for night blindness in RP, but it typically onsets in later childhood.\r\n\r\nIn December 2017, the FDA approved LUXTURNA (voretigene neparvovec-rzyl) gene therapy for the treatment of patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy. The FDA’s conclusion of efficacy is based on improvement in a functional vision score over 1 year in a single open-label controlled Phase 3 study of 31 affected patients. The average age of the 31 randomized patients was 15 years (range 4 to 44 years), including 64% pediatric subjects (n=20, age from 4 to 17 years) and 36% adults (n=11). Functional vision was scored by a patient’s ability to navigate a course in various luminance levels. Using both treated eyes of the 21 subjects in the LUXTURNA treatment group, 11 (52%) had a clinically meaningful score improvement, while only one of the ten (10%) subjects in the control group had a clinically meaningful score improvement. Using the first treated eye only, 15/21 (71%) had a clinically meaningful score improvement, while no comparable score improvement was observed in controls. Other secondary clinical outcomes were also examined. Analysis of white light full-field light sensitivity threshold testing showed statistically significant improvement at 1 year in the LUXTURNA treatment group compared to the control group. The change in visual acuity was not significantly different between the LUXTURNA and control groups.\r\n\r\nLUXTURNA is administered subretinally by injection. Per the FDA package insert, the most common adverse reactions (incidence ≥ 5%) in the clinical trials for LUXTURNA included conjunctival hyperemia, cataract, increased intraocular pressure, retinal tear, dellen (thinning of the corneal stroma), and macular hole. Several other ocular adverse effects were also reported, including risk of endophthalmitis. Safety data was included on the basis of 41 patients (81 eyes).\r\n\r\nFor review: availability of therapy? \nSources: ClinGen","entity_name":"RPE65","entity_type":"gene"},{"created":"2022-12-29T18:32:33.058991+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1727","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: CP as ready","entity_name":"CP","entity_type":"gene"},{"created":"2022-12-29T18:32:33.042420+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1727","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: cp has been classified as Amber List (Moderate Evidence).","entity_name":"CP","entity_type":"gene"},{"created":"2022-12-29T18:32:29.474701+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1727","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: CP were changed from Aceruloplasminaemia to Aceruloplasminaemia, MIM#604290","entity_name":"CP","entity_type":"gene"},{"created":"2022-12-29T18:32:17.011517+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1726","user_name":"Zornitza Stark","item_type":"entity","text":"Tag treatable tag was added to gene: CP.\nTag metabolic tag was added to gene: CP.","entity_name":"CP","entity_type":"gene"},{"created":"2022-12-29T18:32:06.167632+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1726","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: CP: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Aceruloplasminaemia, MIM#604290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"CP","entity_type":"gene"},{"created":"2022-12-29T18:28:16.003963+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1726","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: WT1 as ready","entity_name":"WT1","entity_type":"gene"},{"created":"2022-12-29T18:28:15.992097+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1726","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: wt1 has been classified as Amber List (Moderate Evidence).","entity_name":"WT1","entity_type":"gene"},{"created":"2022-12-29T18:28:12.342832+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1726","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: WT1 were changed from Denys-Drash syndrome; Wilms tumor, type 1; Frasier syndrome to Wilms tumor, type 1, MIM#194070","entity_name":"WT1","entity_type":"gene"},{"created":"2022-12-29T18:27:44.816387+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1725","user_name":"Zornitza Stark","item_type":"entity","text":"Tag for review tag was added to gene: WT1.\nTag cancer tag was added to gene: WT1.\nTag treatable tag was added to gene: WT1.","entity_name":"WT1","entity_type":"gene"},{"created":"2022-12-29T18:27:25.641254+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1725","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: WT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Wilms tumor, type 1, MIM#194070; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"WT1","entity_type":"gene"},{"created":"2022-12-29T18:22:26.632836+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1725","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: ITGB3 as ready","entity_name":"ITGB3","entity_type":"gene"},{"created":"2022-12-29T18:22:26.620804+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1725","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: itgb3 has been classified as Green List (High Evidence).","entity_name":"ITGB3","entity_type":"gene"},{"created":"2022-12-29T18:22:21.484494+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1725","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: ITGB3 as Green List (high evidence)","entity_name":"ITGB3","entity_type":"gene"},{"created":"2022-12-29T18:22:21.467145+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1725","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: itgb3 has been classified as Green List (High Evidence).","entity_name":"ITGB3","entity_type":"gene"},{"created":"2022-12-29T18:22:08.418299+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1724","user_name":"Zornitza Stark","item_type":"entity","text":"gene: ITGB3 was added\ngene: ITGB3 was added to gNBS. Sources: ClinGen\ntreatable, haematological tags were added to gene: ITGB3.\nMode of inheritance for gene: ITGB3 was set to BIALLELIC, autosomal or pseudoautosomal\nPhenotypes for gene: ITGB3 were set to Glanzmann thrombasthenia 2, MIM#\t619267\nReview for gene: ITGB3 was set to GREEN\nAdded comment: Rated as 'strong actionability' in paediatric patients by ClinGen.\r\n\r\nGT can present soon after birth with episodic mucocutaneous bleeding, purpura, petechiae, unprovoked bruising, and excessive bleeding from the umbilical stump or post-circumcision. Major bleeding complications during the neonatal period, such as ICH following delivery are rare. The clinical severity of GT tends to diminish with age, although the bleeding manifestations persist and are life-long. \r\n\r\nRecombinant activated factor VII (rFVIIa) may be considered for patients with: moderate to severe acute bleeding; for treatment of refractory minor bleeds; for prophylaxis in patients with frequent severe bleeds; treatment during minor and major surgery; and in patients who are refractory to platelet transfusion. Some guidelines suggest utilizing rFVIIa as a first line therapy and saving platelet transfusion for more severe or non-responsive bleeds. High doses have been successful, particularly if used early and upfront. rFVIIa in a dose of =80 µg/kg at intervals of 2.5 h or less were observed to be safe and effective in nonsurgical bleeds, minor and major procedures in patients with or without antibodies, and/or refractoriness.\r\n\r\nThe International Glanzmann Thrombasthenia Registry (GTR), published in 2015, studied 184 patients with 829 bleeding episodes and 96 patients with 206 surgical interventions. rFVIIa alone was used in 124/829 bleeds and the proportion of successful treatment to stop bleeding was 91%. In patients without antibodies/refractoriness, rFVIIa, either alone or with antifibrinolytics, and platelets±antifibrinolytics were rated 100% effective for 24 minor and 4 major procedures. The lowest effectiveness of rFVIIa treatment alone was 88.9% (16/18 effective minor procedures) in refractory patients with platelet antibodies.\r\n\r\nDesmopressin (DDAVP) may be considered as an additional treatment for mild bleeding episodes. DDAVP has been shown to be effective in many bleeding disorders, including inherited platelet function disorders. However, DDAVP efficacy among GT patients has not been established and guideline recommendations are conflicting. \nSources: ClinGen","entity_name":"ITGB3","entity_type":"gene"},{"created":"2022-12-29T18:16:40.641360+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1723","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: ITGA2B as ready","entity_name":"ITGA2B","entity_type":"gene"},{"created":"2022-12-29T18:16:40.629485+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1723","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: itga2b has been classified as Green List (High Evidence).","entity_name":"ITGA2B","entity_type":"gene"},{"created":"2022-12-29T18:16:34.165385+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1723","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: ITGA2B as Green List (high evidence)","entity_name":"ITGA2B","entity_type":"gene"},{"created":"2022-12-29T18:16:34.150230+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1723","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: itga2b has been classified as Green List (High Evidence).","entity_name":"ITGA2B","entity_type":"gene"},{"created":"2022-12-29T18:16:16.454079+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1722","user_name":"Zornitza Stark","item_type":"entity","text":"gene: ITGA2B was added\ngene: ITGA2B was added to gNBS. Sources: ClinGen\ntreatable, haematological tags were added to gene: ITGA2B.\nMode of inheritance for gene: ITGA2B was set to BIALLELIC, autosomal or pseudoautosomal\nPhenotypes for gene: ITGA2B were set to Glanzmann thrombasthaenia 1, MIM# 273800\nReview for gene: ITGA2B was set to GREEN\nAdded comment: Rated as 'strong actionability' in paediatric patients by ClinGen.\r\n\r\nGT can present soon after birth with episodic mucocutaneous bleeding, purpura, petechiae, unprovoked bruising, and excessive bleeding from the umbilical stump or post-circumcision. Major bleeding complications during the neonatal period, such as ICH following delivery are rare. The clinical severity of GT tends to diminish with age, although the bleeding manifestations persist and are life-long. \r\n\r\nRecombinant activated factor VII (rFVIIa) may be considered for patients with: moderate to severe acute bleeding; for treatment of refractory minor bleeds; for prophylaxis in patients with frequent severe bleeds; treatment during minor and major surgery; and in patients who are refractory to platelet transfusion. Some guidelines suggest utilizing rFVIIa as a first line therapy and saving platelet transfusion for more severe or non-responsive bleeds. High doses have been successful, particularly if used early and upfront. rFVIIa in a dose of =80 µg/kg at intervals of 2.5 h or less were observed to be safe and effective in nonsurgical bleeds, minor and major procedures in patients with or without antibodies, and/or refractoriness.\r\n\r\nThe International Glanzmann Thrombasthenia Registry (GTR), published in 2015, studied 184 patients with 829 bleeding episodes and 96 patients with 206 surgical interventions. rFVIIa alone was used in 124/829 bleeds and the proportion of successful treatment to stop bleeding was 91%. In patients without antibodies/refractoriness, rFVIIa, either alone or with antifibrinolytics, and platelets±antifibrinolytics were rated 100% effective for 24 minor and 4 major procedures. The lowest effectiveness of rFVIIa treatment alone was 88.9% (16/18 effective minor procedures) in refractory patients with platelet antibodies.\r\n\r\nDesmopressin (DDAVP) may be considered as an additional treatment for mild bleeding episodes. DDAVP has been shown to be effective in many bleeding disorders, including inherited platelet function disorders. However, DDAVP efficacy among GT patients has not been established and guideline recommendations are conflicting. \nSources: ClinGen","entity_name":"ITGA2B","entity_type":"gene"},{"created":"2022-12-29T18:11:33.048576+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1721","user_name":"Zornitza Stark","item_type":"entity","text":"Tag for review was removed from gene: F7.","entity_name":"F7","entity_type":"gene"},{"created":"2022-12-29T18:11:24.920835+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1721","user_name":"Zornitza Stark","item_type":"entity","text":"changed review comment from: Well established gene-disease association.\r\n\r\nVariable severity.\r\n\r\nTreatment: Recombinant coagulation Factor VIIa \r\n\r\nNon-genetic confirmatory testing: factor VII level; to: Well established gene-disease association.\r\n\r\nVariable severity.\r\n\r\nTreatment: Recombinant coagulation Factor VIIa \r\n\r\nNon-genetic confirmatory testing: factor VII level\r\n\r\nRated as 'strong actionability' in paediatric patients by ClinGen.\r\n\r\nClinical expression of factor VII deficiency is highly variable, and no consistent relationship has been found between the severity of the hemorrhagic syndrome and the residual levels of FVII activity. Individuals can be completely asymptomatic despite a very low FVII level. A bleeding history appears more predictive of further bleeding than the factor VII level. Factor VII levels increase during pregnancy, but levels usually remain insufficient for hemostasis in severely affected cases. Individuals with no history of bleeding do not appear to be at increased risk of PPH. Heterozygotes often have approximately half-normal levels of coagulation factors and are often asymptomatic. However, up to 2% of patients with severe bleeding phenotype are heterozygotes.\r\n\r\nConsider prophylaxis using rFVIIa in certain circumstances. Long term prophylaxis should be considered for cases with a personal or family history of severe bleeding or with FVII activity <0.01 IU/ml using rFVIIa, adjusting to maintain clinical response. Short term prophylaxis should be considered for cases for neonates without a personal or family history of severe bleeding but who have FVII activity 0.01-0.05 IU/ml up to 6-12 months of age. ","entity_name":"F7","entity_type":"gene"},{"created":"2022-12-29T17:59:05.760474+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1721","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: ABCC8 as ready","entity_name":"ABCC8","entity_type":"gene"},{"created":"2022-12-29T17:59:05.747731+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1721","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: abcc8 has been classified as Green List (High Evidence).","entity_name":"ABCC8","entity_type":"gene"},{"created":"2022-12-29T17:58:58.605747+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1721","user_name":"Zornitza Stark","item_type":"entity","text":"Tag treatable tag was added to gene: ABCC8.\nTag endocrine tag was added to gene: ABCC8.","entity_name":"ABCC8","entity_type":"gene"},{"created":"2022-12-29T17:58:46.475834+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1721","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: ABCC8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diabetes mellitus, permanent neonatal 3, with or without neurologic features, MIM 618857; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"ABCC8","entity_type":"gene"},{"created":"2022-12-29T17:56:44.292387+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1721","user_name":"Zornitza Stark","item_type":"entity","text":"Tag treatable tag was added to gene: COL9A2.\nTag ophthalmological tag was added to gene: COL9A2.","entity_name":"COL9A2","entity_type":"gene"},{"created":"2022-12-29T17:56:26.647736+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1721","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: COL9A2: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"COL9A2","entity_type":"gene"},{"created":"2022-12-29T17:56:17.024172+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1721","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: COL9A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21671392, 31090205, 33356723; Phenotypes: Stickler syndrome, type V, MIM 614284; Mode of inheritance: None","entity_name":"COL9A2","entity_type":"gene"},{"created":"2022-12-29T17:54:54.073392+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1721","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: COL9A1 as ready","entity_name":"COL9A1","entity_type":"gene"},{"created":"2022-12-29T17:54:54.040716+11:00","panel_name":"gNBS","panel_id":3931,"panel_version":"0.1721","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: col9a1 has been classified as Green List (High Evidence).","entity_name":"COL9A1","entity_type":"gene"}]}