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=621",
"previous": "https://panelapp-aus.org/api/v1/activities/?format=api&page=619",
"results": [
{
"created": "2023-03-29T12:22:44.645365+11:00",
"panel_name": "Baby Screen+ newborn screening",
"panel_id": 3931,
"panel_version": "0.2128",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: JUP: Changed rating: AMBER",
"entity_name": "JUP",
"entity_type": "gene"
},
{
"created": "2023-03-29T12:20:22.618361+11:00",
"panel_name": "Baby Screen+ newborn screening",
"panel_id": 3931,
"panel_version": "0.2128",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: DSP as Amber List (moderate evidence)",
"entity_name": "DSP",
"entity_type": "gene"
},
{
"created": "2023-03-29T12:20:22.607857+11:00",
"panel_name": "Baby Screen+ newborn screening",
"panel_id": 3931,
"panel_version": "0.2128",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: dsp has been classified as Amber List (Moderate Evidence).",
"entity_name": "DSP",
"entity_type": "gene"
},
{
"created": "2023-03-29T12:20:07.751521+11:00",
"panel_name": "Baby Screen+ newborn screening",
"panel_id": 3931,
"panel_version": "0.2127",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "changed review comment from: Screen for bi-allelic disease as can be more severe, earlier onset.; to: Discussed screening for bi-allelic disease as can be more severe, earlier onset.\r\n\r\nAlso discussed with paediatric cardiologist: variable age of onset and penetrance, exclude.",
"entity_name": "DSP",
"entity_type": "gene"
},
{
"created": "2023-03-29T12:19:05.729112+11:00",
"panel_name": "Baby Screen+ newborn screening",
"panel_id": 3931,
"panel_version": "0.2127",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: DSP: Changed rating: AMBER",
"entity_name": "DSP",
"entity_type": "gene"
},
{
"created": "2023-03-29T12:17:36.530249+11:00",
"panel_name": "Bone Marrow Failure",
"panel_id": 56,
"panel_version": "1.32",
"user_name": "Raja Vasireddy",
"item_type": "entity",
"text": "reviewed gene: SRP54: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29914977; Phenotypes: Neutropenia, promyelocytic maturation arrest, neurodevelopmental delay, exocrine pancreatic insuffciency.; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "SRP54",
"entity_type": "gene"
},
{
"created": "2023-03-29T12:15:32.274357+11:00",
"panel_name": "Baby Screen+ newborn screening",
"panel_id": 3931,
"panel_version": "0.2127",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: CASQ2 as Amber List (moderate evidence)",
"entity_name": "CASQ2",
"entity_type": "gene"
},
{
"created": "2023-03-29T12:15:32.266900+11:00",
"panel_name": "Baby Screen+ newborn screening",
"panel_id": 3931,
"panel_version": "0.2127",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: casq2 has been classified as Amber List (Moderate Evidence).",
"entity_name": "CASQ2",
"entity_type": "gene"
},
{
"created": "2023-03-29T12:15:17.746227+11:00",
"panel_name": "Baby Screen+ newborn screening",
"panel_id": 3931,
"panel_version": "0.2126",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "changed review comment from: Well established gene-disease association.\r\n\r\nClinGen: 'strong actionability' both for adult and paediatric patients. Treatment: beta blockers first line; ICD. There are also numerous known arrhythmia triggers which can be avoided.\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\n; to: Well established gene-disease association.\r\n\r\nClinGen: 'strong actionability' both for adult and paediatric patients. Treatment: beta blockers first line; ICD. There are also numerous known arrhythmia triggers which can be avoided.\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\nReviewed with paediatric cardiologist: variable penetrance and age of onset.\r\n\r\n",
"entity_name": "CASQ2",
"entity_type": "gene"
},
{
"created": "2023-03-29T12:14:26.149223+11:00",
"panel_name": "Baby Screen+ newborn screening",
"panel_id": 3931,
"panel_version": "0.2126",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: CASQ2: Changed rating: AMBER",
"entity_name": "CASQ2",
"entity_type": "gene"
},
{
"created": "2023-03-29T12:06:18.963583+11:00",
"panel_name": "Incidentalome",
"panel_id": 126,
"panel_version": "0.223",
"user_name": "Sangavi Sivagnanasundram",
"item_type": "entity",
"text": "changed review comment from: PubMed: 17121991: transgenic mouse study identified that hypoxia increase BACE1 activity which resulted in a significant increase in the production of beta-amyloid in AD-related APP mutations. The study showed that hypoxia up-regulated Bace1 mRNA and increased deposition of beta proteins.\r\n\r\nPMID: 1520398 – V717I variant identified in multiple members in a Canadian family of European decent with a dominant inheritance of Alzheimers disease\r\nPMID: 15365148 – 1 family with 6 affected individuals over 3 generations with heterozygous mutations in APP gene – phenotypic features of Alzheimers. Individuals had MRI conducted showing multiple white matter infarcts along the long penetrating arteries\r\nPubMed: 15668448 – two siblings in an African American family with distinctive features of early-onset AD with APP mutations\r\nPMID: 1671712 - V717I mutation identified in 2 unrelated UK families with Alzheimers disease via a genetic linkage study\r\nPMID: 1678058 – 2 individuals from 2 unrelated Japanese families with early onset Alzheimers disease via a genetic linkage study; to: PubMed: 17121991: transgenic mouse study identified that hypoxia increase BACE1 activity which resulted in a significant increase in the production of beta-amyloid in AD-related APP mutations. The study showed that hypoxia up-regulated Bace1 mRNA leading to an increased deposition of beta proteins.\r\n\r\nPMID: 1520398 – V717I variant identified in multiple members in a Canadian family of European decent with a dominant inheritance of Alzheimers disease\r\nPMID: 15365148 – 1 family with 6 affected individuals over 3 generations with heterozygous mutations in APP gene – phenotypic features of Alzheimers. Individuals had MRI conducted showing multiple white matter infarcts along the long penetrating arteries\r\nPubMed: 15668448 – two siblings in an African American family with distinctive features of early-onset AD with APP mutations\r\nPMID: 1671712 - V717I mutation identified in 2 unrelated UK families with Alzheimers disease via a genetic linkage study\r\nPMID: 1678058 – 2 individuals from 2 unrelated Japanese families with early onset Alzheimers disease via a genetic linkage study",
"entity_name": "APP",
"entity_type": "gene"
},
{
"created": "2023-03-29T12:05:55.333782+11:00",
"panel_name": "Incidentalome",
"panel_id": 126,
"panel_version": "0.223",
"user_name": "Sangavi Sivagnanasundram",
"item_type": "entity",
"text": "reviewed gene: APP: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 17121991, 1520398, 15365148, 15668448, 1671712, 1678058; Phenotypes: Alzheimer's Disease (MIM#104300); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown",
"entity_name": "APP",
"entity_type": "gene"
},
{
"created": "2023-03-29T11:59:47.340636+11:00",
"panel_name": "Baby Screen+ newborn screening",
"panel_id": 3931,
"panel_version": "0.2126",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: CALM1 as Amber List (moderate evidence)",
"entity_name": "CALM1",
"entity_type": "gene"
},
{
"created": "2023-03-29T11:59:47.328394+11:00",
"panel_name": "Baby Screen+ newborn screening",
"panel_id": 3931,
"panel_version": "0.2126",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: calm1 has been classified as Amber List (Moderate Evidence).",
"entity_name": "CALM1",
"entity_type": "gene"
},
{
"created": "2023-03-29T11:59:09.328857+11:00",
"panel_name": "Baby Screen+ newborn screening",
"panel_id": 3931,
"panel_version": "0.2125",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: CALM3 were changed from Ventricular tachycardia, catecholaminergic polymorphic 6 , MIM#\t618782; Long QT syndrome 16, MIM#618782 to Long QT syndrome 16, MIM#618782",
"entity_name": "CALM3",
"entity_type": "gene"
},
{
"created": "2023-03-29T11:58:41.388518+11:00",
"panel_name": "Baby Screen+ newborn screening",
"panel_id": 3931,
"panel_version": "0.2124",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "changed review comment from: 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; to: 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\nExclude for CPVT: association has moderate evidence, there are issues with penetrance, and treatment is generally only recommended in symptomatic individuals.\r\nSources: ClinGen",
"entity_name": "CALM3",
"entity_type": "gene"
},
{
"created": "2023-03-29T11:57:53.105395+11:00",
"panel_name": "Baby Screen+ newborn screening",
"panel_id": 3931,
"panel_version": "0.2124",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: CALM3: Changed phenotypes: Long QT syndrome 16, MIM#618782",
"entity_name": "CALM3",
"entity_type": "gene"
},
{
"created": "2023-03-29T11:57:02.861764+11:00",
"panel_name": "Baby Screen+ newborn screening",
"panel_id": 3931,
"panel_version": "0.2124",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: CALM3: Changed rating: GREEN",
"entity_name": "CALM3",
"entity_type": "gene"
},
{
"created": "2023-03-29T11:56:20.377237+11:00",
"panel_name": "Baby Screen+ newborn screening",
"panel_id": 3931,
"panel_version": "0.2124",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: CALM3: Changed rating: AMBER",
"entity_name": "CALM3",
"entity_type": "gene"
},
{
"created": "2023-03-29T11:56:02.497350+11:00",
"panel_name": "Baby Screen+ newborn screening",
"panel_id": 3931,
"panel_version": "0.2124",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: CALM2 as Amber List (moderate evidence)",
"entity_name": "CALM2",
"entity_type": "gene"
},
{
"created": "2023-03-29T11:56:02.486719+11:00",
"panel_name": "Baby Screen+ newborn screening",
"panel_id": 3931,
"panel_version": "0.2124",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: calm2 has been classified as Amber List (Moderate Evidence).",
"entity_name": "CALM2",
"entity_type": "gene"
},
{
"created": "2023-03-29T11:55:48.767689+11:00",
"panel_name": "Baby Screen+ newborn screening",
"panel_id": 3931,
"panel_version": "0.2123",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "changed review comment from: 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; to: 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\nReviewed with paediatric cardiologist: not for inclusion due to issues with penetrance, plus guidelines only generally recommend treatment is symptomatic individuals.",
"entity_name": "CALM2",
"entity_type": "gene"
},
{
"created": "2023-03-29T11:55:32.033443+11:00",
"panel_name": "Baby Screen+ newborn screening",
"panel_id": 3931,
"panel_version": "0.2123",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: CALM2: Changed rating: AMBER",
"entity_name": "CALM2",
"entity_type": "gene"
},
{
"created": "2023-03-29T11:55:05.081295+11:00",
"panel_name": "Baby Screen+ newborn screening",
"panel_id": 3931,
"panel_version": "0.2123",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "changed review comment from: 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; to: 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\nReviewed with paediatric cardiologist: not for inclusion due to issues with penetrance, plus guidelines only generally recommend treatment is symptomatic individuals.",
"entity_name": "CALM1",
"entity_type": "gene"
},
{
"created": "2023-03-29T11:53:57.129635+11:00",
"panel_name": "Baby Screen+ newborn screening",
"panel_id": 3931,
"panel_version": "0.2123",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: CALM1: Changed rating: AMBER",
"entity_name": "CALM1",
"entity_type": "gene"
},
{
"created": "2023-03-29T11:50:00.446611+11:00",
"panel_name": "Incidentalome",
"panel_id": 126,
"panel_version": "0.223",
"user_name": "Sangavi Sivagnanasundram",
"item_type": "entity",
"text": "reviewed gene: ANG: Rating: GREEN; Mode of pathogenicity: None; Publications: 17886298, 16501576, 18087731, 20301623; Phenotypes: Amyotrophic Lateral Sclerosis (MONDO: 0012753, MIM#611895); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "ANG",
"entity_type": "gene"
},
{
"created": "2023-03-29T10:29:20.747011+11:00",
"panel_name": "Incidentalome",
"panel_id": 126,
"panel_version": "0.223",
"user_name": "Sangavi Sivagnanasundram",
"item_type": "entity",
"text": "reviewed gene: ATP7B: Rating: GREEN; Mode of pathogenicity: None; Publications: 8298639, 9554743, 10790207, 7626145, 16133174; Phenotypes: Wilson Disease (MONDO:0010200, MIM #277900); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "ATP7B",
"entity_type": "gene"
},
{
"created": "2023-03-29T10:27:41.388470+11:00",
"panel_name": "Incidentalome",
"panel_id": 126,
"panel_version": "0.223",
"user_name": "Sangavi Sivagnanasundram",
"item_type": "entity",
"text": "Deleted their review",
"entity_name": "ATP7B",
"entity_type": "gene"
},
{
"created": "2023-03-29T10:26:59.548199+11:00",
"panel_name": "Incidentalome",
"panel_id": 126,
"panel_version": "0.223",
"user_name": "Sangavi Sivagnanasundram",
"item_type": "entity",
"text": "changed review comment from: Well established gene known to be causative of Wilson Disease (Gene Reviews: NBK1512); Loss of function is a well established mechanism - functional study showed impaired production of copper transport and abberant cellular localization of mutant ATP7B proteins – PMID: 16133174; to: Well established gene known to be causative of Wilson Disease (Gene Reviews: NBK1512); Loss of function is a well established mechanism - functional study showed impaired production of copper transport and abberant cellular localization of mutant ATP7B proteins – PMID: 16133174",
"entity_name": "ATP7B",
"entity_type": "gene"
},
{
"created": "2023-03-29T10:26:42.174642+11:00",
"panel_name": "Incidentalome",
"panel_id": 126,
"panel_version": "0.223",
"user_name": "Sangavi Sivagnanasundram",
"item_type": "entity",
"text": "reviewed gene: ATP7B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 8298639, 9554743, 10790207, 7626145, 16133174; Phenotypes: Wilson Disease (MIM#277900); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "ATP7B",
"entity_type": "gene"
},
{
"created": "2023-03-29T09:18:30.239257+11:00",
"panel_name": "Osteogenesis Imperfecta and Osteoporosis",
"panel_id": 147,
"panel_version": "0.106",
"user_name": "Bryony Thompson",
"item_type": "panel",
"text": "Panel name changed from Osteogenesis Imperfecta to Osteogenesis Imperfecta and Osteoporosis",
"entity_name": null,
"entity_type": null
},
{
"created": "2023-03-28T16:26:07.664882+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.38",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: COASY as ready",
"entity_name": "COASY",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:26:07.649666+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.38",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: coasy has been classified as Red List (Low Evidence).",
"entity_name": "COASY",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:26:04.912541+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.38",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: COASY were changed from Neurodegeneration with brain iron accumulation 6 (COPAN); NBIA6 to Neurodegeneration with brain iron accumulation 6, MIM#\t615643",
"entity_name": "COASY",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:25:04.007999+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.37",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: COASY as Red List (low evidence)",
"entity_name": "COASY",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:25:03.988924+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.37",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: coasy has been classified as Red List (Low Evidence).",
"entity_name": "COASY",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:22:47.302480+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.36",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: CA2 were changed from Osteopetrosis, autosomal recessive 3, with renal tubular acidosis, MIM# 259730 to Osteopetrosis, autosomal recessive 3, with renal tubular acidosis, MIM# 259730",
"entity_name": "CA2",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:21:59.209109+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.35",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: CASR as ready",
"entity_name": "CASR",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:21:59.199669+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.35",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: casr has been classified as Green List (High Evidence).",
"entity_name": "CASR",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:21:56.683120+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.35",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: CASR were changed from Hypocalcemia, autosomal dominant; HYPOC1; Hypercalciuric Hypocalcemia; Hypocalcemia, familial to Hypocalcemia, autosomal dominant, MIM# 601198",
"entity_name": "CASR",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:20:44.567816+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.34",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: CASR were set to 32775520; 35402765",
"entity_name": "CASR",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:20:19.240818+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.33",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: CA2 were changed from Osteopetrosis, autosomal recessive 3, with renal tubular acidosis; OPTB3 to Osteopetrosis, autosomal recessive 3, with renal tubular acidosis, MIM# 259730",
"entity_name": "CA2",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:19:54.062991+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.33",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: CASR as Green List (high evidence)",
"entity_name": "CASR",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:19:54.033702+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.33",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: casr has been classified as Green List (High Evidence).",
"entity_name": "CASR",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:19:38.368858+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.32",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: CA2 as ready",
"entity_name": "CA2",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:19:38.356236+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.32",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: ca2 has been classified as Green List (High Evidence).",
"entity_name": "CA2",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:19:19.617588+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.32",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: CASR: Rating: GREEN; Mode of pathogenicity: None; Publications: 8733126, 8813042; Phenotypes: Hypocalcemia, autosomal dominant, MIM# 601198; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "CASR",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:16:30.665906+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.32",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: C1QB were changed from C1q deficiency; C1QD to C1q deficiency, MIM# 613652",
"entity_name": "C1QB",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:16:08.115365+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.32",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: ATN1 as ready",
"entity_name": "ATN1",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:16:08.100739+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.32",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: atn1 has been classified as Red List (Low Evidence).",
"entity_name": "ATN1",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:16:05.249574+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.32",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: CA2 as Green List (high evidence)",
"entity_name": "CA2",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:16:05.219999+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.32",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: ca2 has been classified as Green List (High Evidence).",
"entity_name": "CA2",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:15:30.857835+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.31",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: CA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis, MIM# 259730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "CA2",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:15:06.068579+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.31",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: C1QB as Red List (low evidence)",
"entity_name": "C1QB",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:15:06.053697+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.31",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: c1qb has been classified as Red List (Low Evidence).",
"entity_name": "C1QB",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:14:44.617766+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.30",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: BTD as ready",
"entity_name": "BTD",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:14:44.608848+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.30",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: btd has been classified as Red List (Low Evidence).",
"entity_name": "BTD",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:14:25.509895+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.30",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: C1QB: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: C1q deficiency, MIM# 613652; Mode of inheritance: None",
"entity_name": "C1QB",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:13:09.750467+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.30",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: BTD were changed from Biotinidase Deficiency to Biotinidase deficiency, MIM# 253260",
"entity_name": "BTD",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:12:40.670947+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.29",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: ATN1 were changed from Dentatorubral-pallidoluysian atrophy; DRPLA to Dentatorubral-pallidoluysian atrophy, MIM#\t125370",
"entity_name": "ATN1",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:12:07.857852+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.28",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: BTD as Red List (low evidence)",
"entity_name": "BTD",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:12:07.849914+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.28",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: btd has been classified as Red List (Low Evidence).",
"entity_name": "BTD",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:11:32.701541+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.27",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: BTD: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Biotinidase deficiency, MIM# 253260; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "BTD",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:11:07.292790+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.27",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: ATN1 as Red List (low evidence)",
"entity_name": "ATN1",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:11:07.284992+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.27",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: atn1 has been classified as Red List (Low Evidence).",
"entity_name": "ATN1",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:10:28.701243+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.26",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Tag STR tag was added to gene: ATN1.",
"entity_name": "ATN1",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:09:19.850249+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.26",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: AP1S2 were set to ",
"entity_name": "AP1S2",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:09:07.317026+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.25",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: ACVR1 as ready",
"entity_name": "ACVR1",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:09:07.305003+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.25",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: acvr1 has been classified as Green List (High Evidence).",
"entity_name": "ACVR1",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:08:29.592999+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.25",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: ACVR1 were changed from Fibrodysplasia ossificans progressiva; FOP to Fibrodysplasia ossificans progressiva, MIM# 135100",
"entity_name": "ACVR1",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:08:04.278291+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.25",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: ADAR were set to 23001123; 24262145",
"entity_name": "ADAR",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:06:22.194053+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.24",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: ACVR1 as Green List (high evidence)",
"entity_name": "ACVR1",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:06:22.177511+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.24",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: acvr1 has been classified as Green List (High Evidence).",
"entity_name": "ACVR1",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:05:47.415703+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.23",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: ACVR1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fibrodysplasia ossificans progressiva, MIM# 135100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "ACVR1",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:04:31.282028+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.23",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: ACP5 were changed from Spondyloenchondrodysplasia with immune dysregulation, MIM# 607944 to Spondyloenchondrodysplasia with immune dysregulation, MIM# 607944",
"entity_name": "ACP5",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:04:05.267980+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.23",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: ACP5 were changed from Spondyloenchondrodysplasia, short stature, SLE, intracranial calcification, spasticity, chilblains, autoimmune haemolytic anaemia to Spondyloenchondrodysplasia with immune dysregulation, MIM# 607944",
"entity_name": "ACP5",
"entity_type": "gene"
},
{
"created": "2023-03-28T16:02:53.763472+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.22",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: ACP5: Changed phenotypes: Spondyloenchondrodysplasia with immune dysregulation, MIM# 607944",
"entity_name": "ACP5",
"entity_type": "gene"
},
{
"created": "2023-03-28T15:52:55.013894+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.22",
"user_name": "Yetong Chen",
"item_type": "entity",
"text": "changed review comment from: PMID 17617514 reports a linkage study of AP1S2 in 2 unrelated families with multiple generations affected by Fried syndrome. Cosegregation of the phenotype and AP1S2 variants is demonstrated. Two patients from the French family and 3 patients from the Scottish family developed brain calcification.; to: PMID 17617514 reports a linkage study of AP1S2 in 2 unrelated families with multiple generations affected by Fried syndrome. Cosegregation of the phenotype and AP1S2 variants is demonstrated. Two patients from the French family and 3 patients from the Scottish family developed brain calcification.\r\nPMID 19161147 reports 8 individuals from 2 interrelated Omani families who developed brain calcification.",
"entity_name": "AP1S2",
"entity_type": "gene"
},
{
"created": "2023-03-28T15:45:26.046170+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.22",
"user_name": "Yetong Chen",
"item_type": "entity",
"text": "gene: COASY was added\ngene: COASY was added to Brain Calcification. Sources: Expert list\nMode of inheritance for gene: COASY was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: COASY were set to 27487380; 24360804\nPhenotypes for gene: COASY were set to Neurodegeneration with brain iron accumulation 6 (COPAN); NBIA6\nReview for gene: COASY was set to RED\nAdded comment: There is limited evidence to support a causal role for the COASY gene in brain calcification.\r\nPMID 24360804 demonstrates variants in COASY as a cause of brain iron accumulation, which includes brain calcification, by using segregation analysis. Brain calcification was found in one patient with a homozygous variant of COASY. \nSources: Expert list",
"entity_name": "COASY",
"entity_type": "gene"
},
{
"created": "2023-03-28T14:59:22.513070+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.22",
"user_name": "Yetong Chen",
"item_type": "entity",
"text": "gene: CASR was added\ngene: CASR was added to Brain Calcification. Sources: Expert list\nMode of inheritance for gene: CASR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: CASR were set to 32775520; 35402765\nPhenotypes for gene: CASR were set to Hypocalcemia, autosomal dominant; HYPOC1; Hypercalciuric Hypocalcemia; Hypocalcemia, familial\nReview for gene: CASR was set to RED\nAdded comment: PMID 32775520 reports co-segregation of a CASR variant and intracranial calcification found in 2 patients from the same family.\r\nPMID 35402765 reports a patient with a CASR variant who developed multiple intracerebral calcifications. A pedigree including the patient and her parents can be found in the paper, but CASR genetic testing was not done on the proband's parents so it could not confirm whether the variant is de novo. \nSources: Expert list",
"entity_name": "CASR",
"entity_type": "gene"
},
{
"created": "2023-03-28T13:57:33.284702+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.22",
"user_name": "Yetong Chen",
"item_type": "entity",
"text": "gene: CA2 was added\ngene: CA2 was added to Brain Calcification. Sources: Expert list\nMode of inheritance for gene: CA2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: CA2 were set to 25674028\nPhenotypes for gene: CA2 were set to Osteopetrosis, autosomal recessive 3, with renal tubular acidosis; OPTB3\nReview for gene: CA2 was set to GREEN\nAdded comment: PMID 25674028 reports a female patient with a homozygous variant in the CA2 gene who developed extensive symmetric intracranial calcification.\r\nPMID 22120147 reports brain calcification in 18 individuals, who carry a CA2 variant, from 10 unrelated families. Pedigrees show co-segregation of genotype (homozygous mutant allele) and phenotype. \nSources: Expert list",
"entity_name": "CA2",
"entity_type": "gene"
},
{
"created": "2023-03-28T13:28:17.814224+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "1.92",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: PLXND1 were changed from Congenital heart disease, MONDO:0005453, PLXND1-related to Congenital heart defects, multiple types, 9, MIM# 620294",
"entity_name": "PLXND1",
"entity_type": "gene"
},
{
"created": "2023-03-28T13:28:02.909408+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "1.91",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: PLXND1: Changed phenotypes: Congenital heart defects, multiple types, 9, MIM# 620294",
"entity_name": "PLXND1",
"entity_type": "gene"
},
{
"created": "2023-03-28T13:27:37.424016+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.755",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: PLXND1 were changed from Möbius syndrome, MONDO:0008006; Congenital heart disease, MONDO:0005453, PLXND1-related to Möbius syndrome, MONDO:0008006; Congenital heart defects, multiple types, 9, MIM# 620294",
"entity_name": "PLXND1",
"entity_type": "gene"
},
{
"created": "2023-03-28T13:27:10.769496+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.754",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: PLXND1: Changed phenotypes: Möbius syndrome, Congenital heart defects, multiple types, 9, MIM# 620294",
"entity_name": "PLXND1",
"entity_type": "gene"
},
{
"created": "2023-03-28T13:26:08.835737+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.277",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: PLXND1 were changed from Congenital heart disease, MONDO:0005453, PLXND1-related to Congenital heart defects, multiple types, 9, MIM# 620294",
"entity_name": "PLXND1",
"entity_type": "gene"
},
{
"created": "2023-03-28T13:25:31.230803+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.276",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: PLXND1: Changed phenotypes: Congenital heart defects, multiple types, 9, MIM# 620294",
"entity_name": "PLXND1",
"entity_type": "gene"
},
{
"created": "2023-03-28T13:23:04.513065+11:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.5193",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: AGO1 were changed from Intellectual disability; autism to Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures, MIM# 620292",
"entity_name": "AGO1",
"entity_type": "gene"
},
{
"created": "2023-03-28T13:22:30.918852+11:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.5192",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: AGO1: Changed phenotypes: Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures, MIM# 620292",
"entity_name": "AGO1",
"entity_type": "gene"
},
{
"created": "2023-03-28T13:22:15.159110+11:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1834",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: AGO1 were changed from Neurodevelopmental disorder MONDO:0700092, AGO1-related; non-syndromic ID and seizures to Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures, MIM# 620292",
"entity_name": "AGO1",
"entity_type": "gene"
},
{
"created": "2023-03-28T13:21:36.987910+11:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1833",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: AGO1: Changed phenotypes: Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures, MIM# 620292",
"entity_name": "AGO1",
"entity_type": "gene"
},
{
"created": "2023-03-28T13:21:17.615076+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.754",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: AGO1 were changed from Neurodevelopmental disorder MONDO:0700092, AGO1-related; non-syndromic ID and seizures to Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures, MIM# 620292",
"entity_name": "AGO1",
"entity_type": "gene"
},
{
"created": "2023-03-28T13:20:51.799030+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.753",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: AGO1: Changed phenotypes: Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures, MIM# 620292",
"entity_name": "AGO1",
"entity_type": "gene"
},
{
"created": "2023-03-28T13:19:57.598625+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.753",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: PRDM10 as ready",
"entity_name": "PRDM10",
"entity_type": "gene"
},
{
"created": "2023-03-28T13:19:57.591019+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.753",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: prdm10 has been classified as Red List (Low Evidence).",
"entity_name": "PRDM10",
"entity_type": "gene"
},
{
"created": "2023-03-28T13:19:46.952837+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.753",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: PRDM10 as Red List (low evidence)",
"entity_name": "PRDM10",
"entity_type": "gene"
},
{
"created": "2023-03-28T13:19:46.945146+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.753",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: prdm10 has been classified as Red List (Low Evidence).",
"entity_name": "PRDM10",
"entity_type": "gene"
},
{
"created": "2023-03-28T11:55:49.940150+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.22",
"user_name": "Yetong Chen",
"item_type": "entity",
"text": "gene: C1QB was added\ngene: C1QB was added to Brain Calcification. Sources: Expert list\nMode of inheritance for gene: C1QB was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: C1QB were set to 23651859\nPhenotypes for gene: C1QB were set to C1q deficiency; C1QD\nReview for gene: C1QB was set to RED\nAdded comment: Limited evidence supports a casual role of the C1QB gene in brain calcification.\r\nPMID 23651859 reports a patient with a novel homozygous variant in C1QB who developed bilateral frontal infarcts and basal ganglia calcification. \nSources: Expert list",
"entity_name": "C1QB",
"entity_type": "gene"
},
{
"created": "2023-03-28T11:27:24.881899+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.22",
"user_name": "Yetong Chen",
"item_type": "entity",
"text": "gene: BTD was added\ngene: BTD was added to Brain Calcification. Sources: Expert list\nMode of inheritance for gene: BTD was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: BTD were set to 32734340; 3399084\nPhenotypes for gene: BTD were set to Biotinidase Deficiency\nReview for gene: BTD was set to RED\nAdded comment: PMID 3399084 reports one case of Biotinidase Deficiency with basal ganglia calcification. However, no strong or moderate evidence suggests that variants in the BTN gene can cause brain calcification. \nSources: Expert list",
"entity_name": "BTD",
"entity_type": "gene"
},
{
"created": "2023-03-28T07:03:58.755802+11:00",
"panel_name": "Brain Calcification",
"panel_id": 58,
"panel_version": "1.22",
"user_name": "Yetong Chen",
"item_type": "entity",
"text": "gene: ATN1 was added\ngene: ATN1 was added to Brain Calcification. Sources: Expert list\nMode of inheritance for gene: ATN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: ATN1 were set to 2742549\nPhenotypes for gene: ATN1 were set to Dentatorubral-pallidoluysian atrophy; DRPLA\nReview for gene: ATN1 was set to RED\nAdded comment: PMID 2742549 reports the calcification of the globus pallidus in 4 out of the 10 assessed patients with Haw River Syndrome. Although both Haw River Syndrome and DRPLA are caused by the same expanded CAG repeat in the ATN1 gene, no genetic testing was done on the patients to confirm whether they carried ATN1 variants. \nSources: Expert list",
"entity_name": "ATN1",
"entity_type": "gene"
}
]
}