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"count": 221415,
"next": "https://panelapp-aus.org/api/v1/activities/?format=api&page=517",
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"results": [
{
"created": "2023-11-21T11:12:16.490008+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Joce vd Bergen",
"item_type": "entity",
"text": "gene: PKD1L1 was added\ngene: PKD1L1 was added to Congenital Heart Defect. Sources: Literature\nMode of inheritance for gene: PKD1L1 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: PKD1L1 were set to PMID: 27616478; 31026592; 3079108; 30791085; 33655537\nPhenotypes for gene: PKD1L1 were set to Heterotaxy, visceral, 8, autosomal; HTX8 (MIM617205)\nReview for gene: PKD1L1 was set to GREEN\nAdded comment: Numerous families (6 families, 9 affected individuals) reported with heterotaxy and complex congenital heart defects, with biallelic variants (primarily nonsense, frameshift, splice site and a missense variant) in the PKD1L1 gene. Three reports with additional features (3079108, 30791085, 30791085), such as congenital asplenia, sideroblastic anemia, hydrops fetalis. \r\n\r\nSeveral animal models suggest PKD1L1 plays a significant role in the development of L-R asymmetry and establish the L-R axis in vertebrate organisms, including mouse null and missense substitution models and a medaka knockout. Where complex congenital heart defects are often associated with laterality defects (ranging from situs inversus totalis (SIT) to situs\r\n\r\nClinVar: reports all published variants presented, plus 1 additional nonsense variant (not published). Summary: likely pathogenic/pathogenic (6 nonsense loss of function, 2 splice site and 1 missense variant), associated with autosomal visceral heterotaxy type 8, MIM 617205). \nSources: Literature",
"entity_name": "PKD1L1",
"entity_type": "gene"
},
{
"created": "2023-11-21T10:34:12.044677+11:00",
"panel_name": "Cataract",
"panel_id": 66,
"panel_version": "0.361",
"user_name": "Elena Savva",
"item_type": "entity",
"text": "Publications for gene: DNA2 were set to 37133451",
"entity_name": "DNA2",
"entity_type": "gene"
},
{
"created": "2023-11-21T00:08:09.099678+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Yi-Wei Chao",
"item_type": "entity",
"text": "edited their review of gene: MYBPC3: Changed rating: GREEN",
"entity_name": "MYBPC3",
"entity_type": "gene"
},
{
"created": "2023-11-21T00:06:49.872633+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Yi-Wei Chao",
"item_type": "entity",
"text": "reviewed gene: MYBPC3: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 34097875, 25335496, 31877118, 22057632, 18467358, 36980931, 33209723; Phenotypes: Hypertrophic cardiomyopathy, bicuspid aortic valve, severe infantile cardiomyopathy, septal defect; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal",
"entity_name": "MYBPC3",
"entity_type": "gene"
},
{
"created": "2023-11-20T22:55:19.877482+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Dion Paul",
"item_type": "entity",
"text": "gene: LTBP2 was added\ngene: LTBP2 was added to Congenital Heart Defect. Sources: Literature\nMode of inheritance for gene: LTBP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: LTBP2 were set to 33098376; 35245370; 31512380; 22539340\nPhenotypes for gene: LTBP2 were set to Atrioventricular septal defect (AVSD); Mitral valve prolapse; patent ductus arteriosus (PDA); secondary atrial septal defect; pulmonary hypertension; polydactyly\nPenetrance for gene: LTBP2 were set to unknown\nMode of pathogenicity for gene: LTBP2 was set to Other\nReview for gene: LTBP2 was set to RED\nAdded comment: OMIM (602091) LTBP2 encodes an extracellular matrix (ECM) protein that is expressed in elastic tissues and associates with fibrillin-1 (FBN1) containing microfibrils (PMID: 22539340). Due to this gene's wide association with fibrillin and elastin and corresponding ocular disorders, it is already included in the congenital glaucoma panel.\r\n\r\nAnimal model study - PMID: 31512380 LTBP2 silencing reduces myocardial oxidative stress injury, myocardial fibrosis and myocardial remodelling in rat models of dilated cardiomyopathy (DCM) by down-regulating the NF-κB signalling pathway.\r\n\r\nPMID: 33098376 This study performed whole exome sequencing on a single 1.5-year-old female patient with complex CHD. The phenotype of this patient consisted of the following features: complete atrioventricular septal defect (AVSD), patent ductus arteriosus (PDA), secondary atrial septal defect, pulmonary hypertension, and polydactyly. WES revealed the following heterozygous variant in exon 12 of LTBP2: c.2206G>A (p.Asp736Asn), RefSeq NM_000428.2. Unfortunately, nil family data is available to power family studies. WES also identified another heterozygous variant within the TCTN3 gene. Sanger sequencing was employed to validate the variant. LTBP2 variants are associated with Weill-Marchesani syndrome 3 (WMS3, OMIM #614819), a rare connective tissue disorder characterized by short stature, brachydactyly, joint stiffness, and eye abnormalities. 39% of these patients demonstrate pulmonary and aortic stenosis (PMID: 22539340). Furthermore this study generated human pluripotent stem cell lines (with the aforementioned LTBP2 variant) which differentiated into cardiomyocytes, yielding transcriptomic analysis. Relative to the wildtype, the LTBP2 variant delayed the development of cardiomyocytes and along with the TCTN3 variant may affect contractility of cardiac myocytes and the development of the heart.\r\n\r\nPMID: 33098376 The allele frequency of LTBP2 c.2206G>A was 0.0009, 0.0035 and 0.0008 in population databases of dbSNP, 1000Genomes, and HGVD (BGI). \r\n\r\nPMID: 35245370 Genome-wide association study identified six candidate genes associated with mitral valve prolapse (MVP) - one of which included LTBP2. LTBP2 at 14q24.3 demonstrated high levels of protein expression with RNA-Seq confirming corresponding gene expression as a main driver. Although this study labelled LTBP2 as one of the strongest candidate genes at a particular locus for MVP, it also pinpointed a lack of sufficient concordant evidence. This study suggests TGF-B signalling as a role in isolated MVP pathogenesis - TGF-B signalling is regulated by an extracellular matrix protein encoded by LTBP2. \nSources: Literature",
"entity_name": "LTBP2",
"entity_type": "gene"
},
{
"created": "2023-11-20T22:05:46.816351+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Luke Tork",
"item_type": "entity",
"text": "changed review comment from: Missense variants (and sometimes truncations) in ZFPM2 segregate in individuals with multiple types of congenital heart disease. Development of cardiac related structures involve the GATA family member genes. The ZFPM2 gene encodes the FOG2 protein, a transcriptional regulator responsible for binding to GATA, as well as the deacetylation (NuRD) complex - moderating GATA-mediated gene regulation. Hence, mutations in important residues of ZFPM2 may disrupt FOG2's interaction with GATA4 or NuRD complexes, resulting in congenital heart defects [PMID:28372585]\r\n\r\nPhenotypes such as DIAPHRAGMATIC HERNIA 3; DIH3 [MIM:610187], TETRALOGY OF FALLOT; TOF [MIM:187500], and DOUBLE-OUTLET RIGHT VENTRICLE; DORV [MIM:217095] are commonly seen in patients with pathogenic ZFPM2 variants.; to: Missense variants (and sometimes truncations) in ZFPM2 segregate in individuals with multiple types of congenital heart disease. Development of cardiac related structures involve the GATA family member genes. The ZFPM2 gene encodes the FOG2 protein, a transcriptional regulator responsible for binding to GATA, as well as the deacetylation (NuRD) complex - moderating GATA-mediated gene regulation. Hence, mutations in important residues of ZFPM2 may disrupt FOG2's interaction with GATA4 or NuRD complexes, resulting in congenital heart defects [PMID:28372585]\r\n\r\nPhenotypes such as DIAPHRAGMATIC HERNIA 3; DIH3 [MIM:610187], TETRALOGY OF FALLOT; TOF [MIM:187500], and DOUBLE-OUTLET RIGHT VENTRICLE; DORV [MIM:217095] are commonly seen in patients with ZFPM2 variants.",
"entity_name": "ZFPM2",
"entity_type": "gene"
},
{
"created": "2023-11-20T22:04:56.637383+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Luke Tork",
"item_type": "entity",
"text": "reviewed gene: ZFPM2: Rating: AMBER; Mode of pathogenicity: Other; Publications: 29018978, 25025186, 28372585, 21919901, 24702427; Phenotypes: 217095, 87500, 610187; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal",
"entity_name": "ZFPM2",
"entity_type": "gene"
},
{
"created": "2023-11-20T21:41:43.923172+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Ling Sun",
"item_type": "entity",
"text": "edited their review of gene: THOC6: Changed phenotypes: Beaulieu-Boycott-Innes syndrome (OMIM#613680)",
"entity_name": "THOC6",
"entity_type": "gene"
},
{
"created": "2023-11-20T21:41:33.356863+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Ling Sun",
"item_type": "entity",
"text": "edited their review of gene: THOC6: Changed phenotypes: 613680",
"entity_name": "THOC6",
"entity_type": "gene"
},
{
"created": "2023-11-20T21:41:23.243883+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Ling Sun",
"item_type": "entity",
"text": "changed review comment from: THOC6 homozygous or compound heterozygous variants are associated with Beaulieu-Boycott-Innes syndrome (OMIM#613680). Clinical spectrum is heterogenous, with major phenotype DD and ID (Note that this gene is already on the ID panel). Some are affected with structural cardiac anomalies, therefore not all individuals with BBIS have cardiac anomalies (hence, not a major phenotype, eg. see https://databases.lovd.nl/shared/diseases/03390).\r\n\r\nPMID 35426486: Two siblings with maternally inherited c.[298T>A;700G>T;824G>A], p.[(Trp100Arg);(Val234Leu);(Gly275Asp)] and paternally inherited c.977T>G, p.(Val326Gly) [compound het]\r\n\r\nPMID: 30476144: A boy with mat UPD homozygous c.(298T>A; 700G>C; 824G>C)\r\nA girl with maternally inherited c.(298T>A, 700G>C, 824G>A) and paternally inherited c.569G>A, p.(Gly190Glu) [compount het]\r\n\r\nPMID: 32282736: A boy with paternally inherited c.664T>C (p.Trp222Arg) and maternally inherited c.945+1 G>A [compound het] \r\nSources: Other; to: THOC6 homozygous or compound heterozygous variants are associated with Beaulieu-Boycott-Innes syndrome (OMIM#613680). Clinical spectrum is heterogenous, with major phenotype DD and ID (Note that this gene is already on the ID panel). Some are affected with structural cardiac anomalies, therefore not all individuals with BBIS have cardiac anomalies (hence, not a major phenotype, eg. see https://databases.lovd.nl/shared/diseases/03390).\r\n\r\nPMID 35426486: Two siblings with maternally inherited c.[298T>A;700G>T;824G>A], p.[(Trp100Arg);(Val234Leu);(Gly275Asp)] and paternally inherited c.977T>G, p.(Val326Gly) [compound het]\r\n\r\nPMID: 30476144: A boy with mat UPD homozygous c.(298T>A; 700G>C; 824G>C)\r\nA girl with maternally inherited c.(298T>A, 700G>C, 824G>A) and paternally inherited c.569G>A, p.(Gly190Glu) [compount het]\r\n\r\nPMID: 32282736: A boy with paternally inherited c.664T>C (p.Trp222Arg) and maternally inherited c.945+1 G>A [compound het]\r\n\r\nCardiac anomalies described include VSD/ASD, severe aortic and left ventricular hypoplasia, mild dilation of the right chambers and a mild myocardial hypertrophy secondary to a chronic hypertension, ventriculomegaly \r\n\r\nSources: Other",
"entity_name": "THOC6",
"entity_type": "gene"
},
{
"created": "2023-11-20T21:40:05.358056+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Ling Sun",
"item_type": "entity",
"text": "changed review comment from: THOC6 homozygous or compound heterozygous variants are associated with Beaulieu-Boycott-Innes syndrome. Clinical spectrum is heterogenous, with major phenotype DD and ID (Note that this gene is already on the ID panel). Some are affected with structural cardiac anomalies, therefore not all individuals with BBIS have cardiac anomalies (hence, not a major phenotype, eg. see https://databases.lovd.nl/shared/diseases/03390).\r\n\r\nPMID 35426486: Two siblings with maternally inherited c.[298T>A;700G>T;824G>A], p.[(Trp100Arg);(Val234Leu);(Gly275Asp)] and paternally inherited c.977T>G, p.(Val326Gly) [compound het]\r\n\r\nPMID: 30476144: A boy with mat UPD homozygous c.(298T>A; 700G>C; 824G>C)\r\nA girl with maternally inherited c.(298T>A, 700G>C, 824G>A) and paternally inherited c.569G>A, p.(Gly190Glu) [compount het]\r\n\r\nPMID: 32282736: A boy with paternally inherited c.664T>C (p.Trp222Arg) and maternally inherited c.945+1 G>A [compound het] \nSources: Other; to: THOC6 homozygous or compound heterozygous variants are associated with Beaulieu-Boycott-Innes syndrome (OMIM#613680). Clinical spectrum is heterogenous, with major phenotype DD and ID (Note that this gene is already on the ID panel). Some are affected with structural cardiac anomalies, therefore not all individuals with BBIS have cardiac anomalies (hence, not a major phenotype, eg. see https://databases.lovd.nl/shared/diseases/03390).\r\n\r\nPMID 35426486: Two siblings with maternally inherited c.[298T>A;700G>T;824G>A], p.[(Trp100Arg);(Val234Leu);(Gly275Asp)] and paternally inherited c.977T>G, p.(Val326Gly) [compound het]\r\n\r\nPMID: 30476144: A boy with mat UPD homozygous c.(298T>A; 700G>C; 824G>C)\r\nA girl with maternally inherited c.(298T>A, 700G>C, 824G>A) and paternally inherited c.569G>A, p.(Gly190Glu) [compount het]\r\n\r\nPMID: 32282736: A boy with paternally inherited c.664T>C (p.Trp222Arg) and maternally inherited c.945+1 G>A [compound het] \r\nSources: Other",
"entity_name": "THOC6",
"entity_type": "gene"
},
{
"created": "2023-11-20T21:33:16.222116+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1377",
"user_name": "Ling Sun",
"item_type": "entity",
"text": "Deleted their review",
"entity_name": "THOC6",
"entity_type": "gene"
},
{
"created": "2023-11-20T21:33:08.398640+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1377",
"user_name": "Ling Sun",
"item_type": "entity",
"text": "Deleted their comment",
"entity_name": "THOC6",
"entity_type": "gene"
},
{
"created": "2023-11-20T21:32:59.591995+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Ling Sun",
"item_type": "entity",
"text": "gene: THOC6 was added\ngene: THOC6 was added to Congenital Heart Defect. Sources: Other\nMode of inheritance for gene: THOC6 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: THOC6 were set to 35426486; 30476144; 32282736\nPhenotypes for gene: THOC6 were set to VSD/ASD; severe aortic and left ventricular hypoplasia; Mild dilation of the right chambers and a mild myocardial hypertrophy secondary to a chronic hypertension; ventriculomegaly\nPenetrance for gene: THOC6 were set to Incomplete\nReview for gene: THOC6 was set to AMBER\nAdded comment: THOC6 homozygous or compound heterozygous variants are associated with Beaulieu-Boycott-Innes syndrome. Clinical spectrum is heterogenous, with major phenotype DD and ID (Note that this gene is already on the ID panel). Some are affected with structural cardiac anomalies, therefore not all individuals with BBIS have cardiac anomalies (hence, not a major phenotype, eg. see https://databases.lovd.nl/shared/diseases/03390).\r\n\r\nPMID 35426486: Two siblings with maternally inherited c.[298T>A;700G>T;824G>A], p.[(Trp100Arg);(Val234Leu);(Gly275Asp)] and paternally inherited c.977T>G, p.(Val326Gly) [compound het]\r\n\r\nPMID: 30476144: A boy with mat UPD homozygous c.(298T>A; 700G>C; 824G>C)\r\nA girl with maternally inherited c.(298T>A, 700G>C, 824G>A) and paternally inherited c.569G>A, p.(Gly190Glu) [compount het]\r\n\r\nPMID: 32282736: A boy with paternally inherited c.664T>C (p.Trp222Arg) and maternally inherited c.945+1 G>A [compound het] \nSources: Other",
"entity_name": "THOC6",
"entity_type": "gene"
},
{
"created": "2023-11-20T21:30:27.641770+11:00",
"panel_name": "Overgrowth",
"panel_id": 151,
"panel_version": "1.9",
"user_name": "Ling Sun",
"item_type": "entity",
"text": "Deleted their review",
"entity_name": "MED12",
"entity_type": "gene"
},
{
"created": "2023-11-20T21:30:22.045404+11:00",
"panel_name": "Overgrowth",
"panel_id": 151,
"panel_version": "1.9",
"user_name": "Ling Sun",
"item_type": "entity",
"text": "Deleted their comment",
"entity_name": "MED12",
"entity_type": "gene"
},
{
"created": "2023-11-20T21:30:14.772213+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Ling Sun",
"item_type": "entity",
"text": "gene: MED12 was added\ngene: MED12 was added to Congenital Heart Defect. Sources: Other\nMode of inheritance for gene: MED12 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)\nPublications for gene: MED12 were set to 32682435; 18973276; 31255603; 28724790; 20301719\nPhenotypes for gene: MED12 were set to Dilated cardiomyopathy (DCM); left ventricular non-compaction (LVNC); dilated cardiomyopathy (DCM); arrhythmia; ventricular septal defect (VSD)\nPenetrance for gene: MED12 were set to unknown\nMode of pathogenicity for gene: MED12 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments\nReview for gene: MED12 was set to AMBER\nAdded comment: MED12-associated syndromes or genetic conditions resulting from MED12 loss of function variants can encompass aortic and heart conditions within their broader diagnostic spectrum. For instance, while not universally present in all individuals with Lujan-Fryns syndrome, some may indeed exhibit heart abnormalities as an integral part of their overall clinical profile (PMID: 18973276). Additionally, congenital heart defects and aortic dilation have been sporadically reported in patients with MED12-syndromic XLID. However, these cardiac issues tend to be more consistently observed in females with Hardikar syndrome, with aortic coarctation being the most prevalent cardiac abnormality in this group (PMID: 20301719).\r\n\r\nMoreover, research has demonstrated that mice with a cardiac-specific deletion of the Med12 gene experience disruptions in calcium cycling, disturbances in cardiac electrical activity, and ultimately develop dilated cardiomyopathy (PMID: 2872470). This suggests a critical role for MED12 in cardiac function and highlights its relevance in both research and clinical contexts.\r\n\r\n[Submitted on behalf of Essra Bartlett 20/11/2023] \nSources: Other",
"entity_name": "MED12",
"entity_type": "gene"
},
{
"created": "2023-11-20T20:28:00.378146+11:00",
"panel_name": "Systemic Autoinflammatory Disease_Periodic Fever",
"panel_id": 238,
"panel_version": "1.28",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: ARPC5 as ready",
"entity_name": "ARPC5",
"entity_type": "gene"
},
{
"created": "2023-11-20T20:28:00.364926+11:00",
"panel_name": "Systemic Autoinflammatory Disease_Periodic Fever",
"panel_id": 238,
"panel_version": "1.28",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: arpc5 has been classified as Green List (High Evidence).",
"entity_name": "ARPC5",
"entity_type": "gene"
},
{
"created": "2023-11-20T20:27:56.452820+11:00",
"panel_name": "Systemic Autoinflammatory Disease_Periodic Fever",
"panel_id": 238,
"panel_version": "1.28",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: ARPC5 as Green List (high evidence)",
"entity_name": "ARPC5",
"entity_type": "gene"
},
{
"created": "2023-11-20T20:27:56.445092+11:00",
"panel_name": "Systemic Autoinflammatory Disease_Periodic Fever",
"panel_id": 238,
"panel_version": "1.28",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: arpc5 has been classified as Green List (High Evidence).",
"entity_name": "ARPC5",
"entity_type": "gene"
},
{
"created": "2023-11-20T20:27:26.852950+11:00",
"panel_name": "Systemic Autoinflammatory Disease_Periodic Fever",
"panel_id": 238,
"panel_version": "1.27",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "gene: ARPC5 was added\ngene: ARPC5 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature\nMode of inheritance for gene: ARPC5 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: ARPC5 were set to 37349293; 37382373\nPhenotypes for gene: ARPC5 were set to Immunodeficiency 133 with autoimmunity and autoinflammation, MIM# 620565\nReview for gene: ARPC5 was set to GREEN\nAdded comment: Four individuals from 3 families reported. In addition to recurrent infections, features of autoinflammation common: haemolytic anaemia, thrombocytopenia, hepatosplenomegaly, leukocytosis, neutrophilia, and elevated acute phase reactants. More variable systemic features may include coeliac disease or enteropathy, ileus, nephropathy, eczema, and dermatomyositis. \nSources: Literature",
"entity_name": "ARPC5",
"entity_type": "gene"
},
{
"created": "2023-11-20T20:25:42.010927+11:00",
"panel_name": "Combined Immunodeficiency",
"panel_id": 223,
"panel_version": "1.51",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: ARPC5 were changed from Combined immunodeficiency, ARPC5-related MONDO:0015131 to Immunodeficiency 133 with autoimmunity and autoinflammation, MIM# 620565",
"entity_name": "ARPC5",
"entity_type": "gene"
},
{
"created": "2023-11-20T20:25:07.365222+11:00",
"panel_name": "Combined Immunodeficiency",
"panel_id": 223,
"panel_version": "1.50",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: ARPC5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 133 with autoimmunity and autoinflammation, MIM# 620565; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "ARPC5",
"entity_type": "gene"
},
{
"created": "2023-11-20T20:24:28.584083+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1377",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: ARPC5 were changed from Combined immunodeficiency, ARPC5-related MONDO:0015131 to Immunodeficiency 133 with autoimmunity and autoinflammation, MIM# 620565",
"entity_name": "ARPC5",
"entity_type": "gene"
},
{
"created": "2023-11-20T20:24:02.978191+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1376",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "commented on gene: ARPC5: Features of autoinflammation common: haemolytic anaemia, thrombocytopenia, hepatosplenomegaly, leukocytosis, neutrophilia, and elevated acute phase reactants. More variable systemic features may include coeliac disease or enteropathy, ileus, nephropathy, eczema, and dermatomyositis.",
"entity_name": "ARPC5",
"entity_type": "gene"
},
{
"created": "2023-11-20T20:23:01.440504+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1376",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: ARPC5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 133 with autoimmunity and autoinflammation, MIM# 620565; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "ARPC5",
"entity_type": "gene"
},
{
"created": "2023-11-20T17:24:55.056163+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Penny Snell",
"item_type": "entity",
"text": "changed review comment from: Well established gene-disease association.\r\nCardiofaciocutaneous and Noonan syndromes present with overlapping clinical features, including congenital heart defects.\r\n\r\nThere is limited evidence for loss-of-function as a mechanism of disease for either of these phenotypes.; to: Well established gene-disease association.\r\nCardiofaciocutaneous and Noonan syndromes present with overlapping clinical features, including congenital heart defects.\r\n\r\nThere is limited evidence for loss-of-function as a mechanism of disease for either of these phenotypes.",
"entity_name": "BRAF",
"entity_type": "gene"
},
{
"created": "2023-11-20T17:24:27.178662+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Penny Snell",
"item_type": "entity",
"text": "reviewed gene: BRAF: 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: PMID: 19206169, 18042262; Phenotypes: Cardiofaciocutaneous syndrome, 115150, Noonan syndrome 7, 613706; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "BRAF",
"entity_type": "gene"
},
{
"created": "2023-11-20T16:03:24.007966+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Sivaranjani Balachander",
"item_type": "entity",
"text": "reviewed gene: GATA6: Rating: GREEN; Mode of pathogenicity: None; Publications: (PMID: 22158542, 23223019, 23635550); Phenotypes: Congenital heart defects pancreatic agenesis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown",
"entity_name": "GATA6",
"entity_type": "gene"
},
{
"created": "2023-11-20T15:48:45.276035+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Uditi Shah",
"item_type": "entity",
"text": "reviewed gene: JAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26580007, 19325125, 11139239, 9207787, 9585603, 11152664, 32065591, 12022040, 20437614, 36400760); Phenotypes: ?Deafness, congenital heart defects, and posterior embryotoxon #617992, Alagille syndrome 1 #118450, Charcot-Marie-Tooth disease, axonal, type 2HH #619574, Tetralogy of Fallot #187500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "JAG1",
"entity_type": "gene"
},
{
"created": "2023-11-20T15:43:45.786450+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Uditi Shah",
"item_type": "entity",
"text": "Deleted their review",
"entity_name": "JAG1",
"entity_type": "gene"
},
{
"created": "2023-11-20T15:43:28.165797+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Uditi Shah",
"item_type": "entity",
"text": "changed review comment from: JAG1 is a gene that plays a crucial role in capillary morphogenesis, mesenchymal stem cell differentiation into cardiomyocytes, and the regulation of signaling pathways such as Notch and Wnt.\r\n\r\nMutations in the JAG1 gene are associated with Alagille Syndrome (ALGS), a disorder characterized by liver, heart, and other organ abnormalities. ALGS exhibits high genetic heterogeneity, with various types of mutations identified, including deletions, insertions, splice site mutations, and missense mutations. The majority of ALGS cases involve haploinsufficiency, where a single functional copy of the JAG1 gene is insufficient for normal development. However, some missense mutations may act in a dominant-negative manner, inhibiting Notch signaling.\r\n\r\nIn TOF, a missense mutation in JAG1 was identified in a kindred segregating autosomal dominant TOF with variable expressivity and characteristic facial features.\r\n\r\nJAG1 mutations in axonal Charcot-Marie-Tooth disease type 2HH were associated with impaired peripheral nerve integrity and altered Notch signaling.\r\n\r\nAnother syndrome, DCHE, involving hearing loss, congenital heart defects, and posterior embryotoxon, was also linked to a JAG1 missense mutation. (PMID: 12022040 PMID: 20437614 PMID: 36400760); to: JAG1 is a gene that plays a crucial role in capillary morphogenesis, mesenchymal stem cell differentiation into cardiomyocytes, and the regulation of signaling pathways such as Notch and Wnt. (PMID: 26580007, PMID: 19325125)\r\n\r\nMutations in the JAG1 gene are associated with Alagille Syndrome (ALGS), a disorder characterized by liver, heart, and other organ abnormalities. ALGS exhibits high genetic heterogeneity, with various types of mutations identified, including deletions, insertions, splice site mutations, and missense mutations. The majority of ALGS cases involve haploinsufficiency, where a single functional copy of the JAG1 gene is insufficient for normal development. However, some missense mutations may act in a dominant-negative manner, inhibiting Notch signaling. (PMID: 11139239, PMID: 9207787, PMID: 9585603)\r\n\r\nIn TOF, a missense mutation in JAG1 was identified in a kindred segregating autosomal dominant TOF with variable expressivity and characteristic facial features. (PMID: 11152664)\r\n\r\nJAG1 mutations in axonal Charcot-Marie-Tooth disease type 2HH were associated with impaired peripheral nerve integrity and altered Notch signaling. (PMID: 32065591)\r\n\r\nAnother syndrome, DCHE, involving hearing loss, congenital heart defects, and posterior embryotoxon, was also linked to a JAG1 missense mutation. (PMID: 12022040 PMID: 20437614 PMID: 36400760)",
"entity_name": "JAG1",
"entity_type": "gene"
},
{
"created": "2023-11-20T15:38:45.099026+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Uditi Shah",
"item_type": "entity",
"text": "reviewed gene: JAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 12022040 PMID: 20437614 PMID: 36400760; Phenotypes: ?Deafness, congenital heart defects, and posterior embryotoxon #617992, Alagille syndrome 1 #118450, Charcot-Marie-Tooth disease, axonal, type 2HH #619574, Tetralogy of Fallot #187500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "JAG1",
"entity_type": "gene"
},
{
"created": "2023-11-20T15:32:51.900580+11:00",
"panel_name": "Overgrowth",
"panel_id": 151,
"panel_version": "1.9",
"user_name": "Ling Sun",
"item_type": "entity",
"text": "reviewed gene: MED12: Rating: AMBER; Mode of pathogenicity: None; Publications: 32682435, 18973276, 31255603, 28724790, 20301719; Phenotypes: Dilated cardiomyopathy (DCM), left ventricular non-compaction (LVNC), dilated cardiomyopathy (DCM), arrhythmia, ventricular septal defect (VSD); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)",
"entity_name": "MED12",
"entity_type": "gene"
},
{
"created": "2023-11-20T14:57:03.536097+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "GORJANA ROBEVSKA",
"item_type": "entity",
"text": "gene: NUP188 was added\ngene: NUP188 was added to Congenital Heart Defect. Sources: Literature\nMode of inheritance for gene: NUP188 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: NUP188 were set to PMID: 32021605; 32275884\nPhenotypes for gene: NUP188 were set to Sandestig-Stefanova syndrome MIM 618804\nReview for gene: NUP188 was set to GREEN\nAdded comment: Sandestig et al 2020/19: \r\ntwo unrelated female infants from consanguineous families, each with homozygous nonsense gene variants of NUP188 (p.Tyr96* and p.Gln113*, respectively). Both patients showed close similarity and specificity of clinical features including the course of the disease and a poor prognosis. \r\n\r\nMuir et al 2020: \r\nFour unrelated families with six affected female infants with bi-allelic truncating variants in NUP188. all found to have very similar phenotypes\r\nFunctional studies showed:\r\n1. Nuclear import of proteins was decreased in affected individuals’ fibroblasts, supporting a possible disease mechanism. \r\n2. CRISPR-mediated knockout of NUP188 in Drosophila revealed motor deficits and seizure susceptibility, partially recapitulating the neurological phenotype seen in affected individuals. \r\n3. Removal of NUP188 also resulted in aberrant dendrite tiling, suggesting a potential role of NUP188 in dendritic development \r\n\r\nKey clinical features of Sandestig-Stefanova syndrome MIM 618804: \r\n- congenital cataracts\r\n- hypotonia, \r\n- prenatal-onset ventriculomegaly, \r\n- white-matter abnormalities, \r\n- hypoplastic corpus callosum, \r\n- congenital heart defects, and \r\n- central hypoventilation. \r\nCharacteristic dysmorphic features include: \r\n- small palpebral fissures, \r\n- a wide nasal bridge and nose, \r\n- micrognathia, and \r\n- digital anomalies. \nSources: Literature",
"entity_name": "NUP188",
"entity_type": "gene"
},
{
"created": "2023-11-20T12:59:33.314233+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Arthur Limawan",
"item_type": "entity",
"text": "reviewed gene: CHST14: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ehlers-Danlos syndrome, arterial septal defects, coarctation of the aorta, patent ductus arteriosus, dextrocardia, tricuspid atresia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "CHST14",
"entity_type": "gene"
},
{
"created": "2023-11-20T12:53:42.038114+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Emma Northrop",
"item_type": "entity",
"text": "gene: MAP3K7 was added\ngene: MAP3K7 was added to Congenital Heart Defect. Sources: Other\nMode of inheritance for gene: MAP3K7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: MAP3K7 were set to PMID: 27426734; 29467388; 35730652; 27426733\nPhenotypes for gene: MAP3K7 were set to Cardiospondylocarpofacial syndrome (CSCF) MIM# 157800; Frontometaphyseal dysplasia 2 (FMD2) MIM# 617137\nReview for gene: MAP3K7 was set to GREEN\nAdded comment: CSCF - primarily caused by loss of function variants.\r\nFMD2 - primarily caused by gain of function variants.\r\n\r\nPMID: 27426734 - Monoallelic missense and in-frame deletion variants were identified in the MAP3K7 gene in six individuals affected with CSCF from four unrelated families. All met the clinical feature criteria of CSCF, including skeletal and facial features, and cardiac defects (including VSD (1/6), ASD (1/6) and valve dysplasia (6/6)). One family with 3 affected individuals across 2 generations was reported.\r\n\r\nPMID: 29467388 - One case with a splice variant creating a new splice acceptor site causing an in-frame insertion of 2 amino acids. A heart ultrasound at birth revealed patent foramen ovale with left-right shunt and two small muscular ventricular septal defects, mitral and tricuspid valves dysplasia and mild, non-progressive aortic arch hypoplasia.\r\n\r\nPMID: 35730652 - 14 novel patients with CSCF + 2 with FMD2. 9/15 with Congenital Heart Defects (including the 2 cases with FMD2), 2/12 Ventricular septal defects, 1/13 Atrial septal defects, 4/14 Cardiomyopathy. CSCF cases include one family with 2 individuals across 2 generations. \nSources: Other",
"entity_name": "MAP3K7",
"entity_type": "gene"
},
{
"created": "2023-11-20T11:04:07.147132+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Mary Huang",
"item_type": "entity",
"text": "reviewed gene: ARID1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 33803261; Phenotypes: Coffin-Siris syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "ARID1A",
"entity_type": "gene"
},
{
"created": "2023-11-20T00:18:05.642012+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Rajini Sreenivasan",
"item_type": "entity",
"text": "reviewed gene: CRELD1: Rating: RED; Mode of pathogenicity: None; Publications: (PMID: 22740159, 12632326, 23040494, 25328912, 24697899, 33773999); Phenotypes: Atrioventricular septal defect, susceptibility to, 2, Atrioventricular septal defect, partial, with heterotaxy syndrome MIM#606217; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown",
"entity_name": "CRELD1",
"entity_type": "gene"
},
{
"created": "2023-11-19T17:16:07.366946+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Jen Malcolm",
"item_type": "entity",
"text": "gene: PIGV was added\ngene: PIGV was added to Congenital Heart Defect. Sources: Other\nMode of inheritance for gene: PIGV was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: PIGV were set to PMID: 37372388; 24129430; 37390992; 20802478\nPhenotypes for gene: PIGV were set to mental retardation; seizures and hypotonia; hyperphosphatasia; facial dysmorphism; variable degrees of brachytelephalangy\nPenetrance for gene: PIGV were set to unknown\nMode of pathogenicity for gene: PIGV was set to Other\nReview for gene: PIGV was set to RED\nAdded comment: Autosomal recessive. Multiple variants involved in Mabry syndrome (also known as Hyperphosphatasia)- intellectual disability, distinctive facial features, increased levels of an enzyme called alkaline phosphatase in the blood and other signs and symptoms. \r\nLiterature:\r\n•\tXue et al PMID: 27177984 2 Chinese infants with Mabry syndrome variants PIGV:c.615C>G (p.Asn205Lys) and c.854A>G (p.Tyr285Cys)\r\n•\tThompson et al, PMID: 22315194\r\n 3 patients (2 sibs with compound heterozygotes for c.467G > A and c.494C > A (novel variant) in exon 3 of PIGV gene. 3rd unrelated individual compound heterozygote for the known c.1022C > A/c.1022C > T (p.Ala341Glu/p.Ala341Val) mutation)\r\n•\tHutny et al PMID: 37372388, 6 Polish Patients all with homozygotic mutation (c.1022C>A; p.Ala341Glu) variant hyperphosphatasia with impaired intellectual development syndrome 1 (HPMRS1), distinct from other CDGs in terms of hyperphosphatemia related to abnormal ALP activity and brachytelephalangy.\r\n•\tHorn et al PMID: 24129430\r\n16 individuals with Mabrys syndrome, most common variant c.1022C>A , and also novel variants (c. 176T>G, c.53G>A, c.905T>C, and c.1405C>T) detected PIGV mutations and demonstrate that the severe end of the clinical spectrum presents as a multiple congenital malformation syndrome with a high frequency of Hirschsprung disease, vesicoureteral, and renal anomalies as well as anorectal malformations. PIGV mutations are the major cause of HPMRS, which displays a broad clinical variability regarding associated malformations and growth patterns. Severe developmental delays, particular facial anomalies, brachytelephalangy, and hyperphosphatasia are consistently found in PIGV-positive individuals.\r\nNo evidence of congenital heart defects found. \nSources: Other",
"entity_name": "PIGV",
"entity_type": "gene"
},
{
"created": "2023-11-19T16:24:39.396276+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Dee Lawlor",
"item_type": "entity",
"text": "reviewed gene: KDR: Rating: AMBER; Mode of pathogenicity: None; Publications: 34113005; Phenotypes: Tetralogy of Fallot; Mode of inheritance: Unknown",
"entity_name": "KDR",
"entity_type": "gene"
},
{
"created": "2023-11-19T16:19:38.303227+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Dee Lawlor",
"item_type": "entity",
"text": "Deleted their review",
"entity_name": "KDR",
"entity_type": "gene"
},
{
"created": "2023-11-19T16:18:38.663547+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Dee Lawlor",
"item_type": "entity",
"text": "reviewed gene: KDR: Rating: AMBER; Mode of pathogenicity: None; Publications: 34113005; Phenotypes: ; Mode of inheritance: Unknown",
"entity_name": "KDR",
"entity_type": "gene"
},
{
"created": "2023-11-19T15:58:00.152692+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Harshini Thiyagarajah",
"item_type": "entity",
"text": "reviewed gene: PIGL: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22444671; Phenotypes: colobomas, heart defects, ichthyosiform dermatosis, intellectual disability, ear anomalies; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "PIGL",
"entity_type": "gene"
},
{
"created": "2023-11-19T15:14:43.083021+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Lucas Mitchell",
"item_type": "entity",
"text": "gene: WASHC5 was added\ngene: WASHC5 was added to Congenital Heart Defect. Sources: ClinGen,Literature\nMode of inheritance for gene: WASHC5 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: WASHC5 were set to PMID: 24065355; 37840956; 30896870; 32349777; 32349777\nPhenotypes for gene: WASHC5 were set to Ritscher-Schinzel syndrome - MIM#220210; Ventricular septal defect; Atrial septal defect; Tetralogy of Fallot; Double outlet right ventricle; Hypoplastic left heart; Aortic stenosis; Pulmonic stenosis\nPenetrance for gene: WASHC5 were set to unknown\nReview for gene: WASHC5 was set to AMBER\nAdded comment: Homozygous/biallelic variants in WASHC5 (previous name KIAA0196) are associated with Ritscher-Schinzel syndrome (RSS) - A developmental malformation syndrome characterised by craniofacial abnormalities, congenital heart defects, and cerebellar brain malformations. Cardiac defects include septal defects and aortic stenosis, among others (OMIM: Leonardi et al., 2001; Elliott et al., 2013).\r\n\r\nVictor Chang CHD gene registry reports on WASHC5, also stating unknown penetrance. \r\n(https://chdgene.victorchang.edu.au/gene/9897) \r\n\r\nLiterature (humans):\r\nElliot et al, 2013 (24065355)\r\n8 first nations patients, and 8 of their parents, and 5 unaffected people from same geographic region (northern Manitoba, Canada) underwent homozygosity mapping by SNP array and sanger sequencing. Variable phenotypic traits among affected members included atrial and ventricular septal defects. The only biallelic mutations identified occurred in KIAA0196 (WASHC5), where sequence analysis revealed homozygosity for three novel variants (c.3335+2T>A, c.3335 +4C>A and c.3335+8A>G) in each patient (figure 2A). All parents were heterozygous for the three sequence changes, and none of the five control subjects was homozygous for any of these changes. Comparison of normalised cycle threshold (Ct) values indicated a 6.98 to 8.72 (mean 7.85)-fold reduction in the relative amount of KIAA0196 transcript in the patient samples versus the control sample. Sanger sequencing of the cloned PCR product from a patient revealed that the primary product did not contain exon 27 (figure 2B). Suggesting altered KIAA0196 transcript produced by the patient might be targeted for nonsense mediated decay. Strumpellin, the product of KIAA0196, is a highly conserved glycoprotein from plants to humans, and ubiquitously expressed. \r\n\r\nHarvey et al, 2023 (37840956), reports 2 probands with WASHC5 variants and CHD phenotype. Not clear if probands related, or from same geographical area. Zygosity not clear. No information provided about probands, family testing/segregation. \r\nLandis 2023, (37681527) a cohort of 1362 with CHD, reports one with variant in WASHC5. No further information provided about variant, zygosity, or about participant in paper or supp data. \r\nBu. 2020 et al, (30896870)\r\nReports, 9mnth male in Changsha, China, with patent ductus arteriosus (PDA) - an opening between two blood vessels leading from the heart, patent foramen ovale (PFO) - hole between the left and right atria, and KIAA0196 (WASHC5) variant. No mention zygosity or biallelic. No supp data provided. \r\nMøller Nielsen, 2021(https://doi.org/10.1016/j.ijcchd.2021.100164), \r\nDanish cohort study with Atrial septal defects (ASD), 384 variants identified, three WASHC5 variants are considered pathogenic. Supplementary table 3 reports three WASHC5 variants, but no further information is provided about participants, zygosity of variants, or if blood-related. Limitations state only had singleton data and unable to clarify inheritance/de-novo. Supplementary table reported further info for the three WASHC5 variants, but no explicit mention if biallelic mutations. Excel column J reports 'reads (Ref:Alt)' and indicates participants are ?heterozygous variants which may conflict with RSS being a recessive/biallelic condition? \r\nHseih, 2020, (32349777)\r\nMentioned having two damaging germline and one mosaic mutations in their cohort that supports WASHC5 to be a candidate CHD gene. No further information about those variants or participants is provided. No supp data provided. \r\n\r\nAnimal models:\r\nMouse Genome Informatics MGI#2146110) : Homozygous knockout mice die well prior to E13.5 as no evidence of conceptus. In heterozygous knockout mice no cardiovascular defect recorded.\r\nBu, 2020 (32417190)\r\nMouse and zebrafish studies show potential evidence for WASHC5 biallelic variants cause CHD/. However CliniGen Commented \"neither provide evidence to support the gene-disease relationship (Bu et al., PMID:32417190)\"\r\n\r\n\r\nIn summary, Elliot et al provides detailed evidence, however looking further at recent literature, studies mention or report on WASHC5 variants and possible associations with CHD, but do not report enough detail to be confident and satisfy ClinGene/PanelApp criteria. \nSources: ClinGen, Literature",
"entity_name": "WASHC5",
"entity_type": "gene"
},
{
"created": "2023-11-19T15:09:15.317002+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Harshini Thiyagarajah",
"item_type": "entity",
"text": "gene: PIGL was added\ngene: PIGL was added to Congenital Heart Defect. Sources: Literature\nMode of inheritance for gene: PIGL was set to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "PIGL",
"entity_type": "gene"
},
{
"created": "2023-11-19T12:51:25.676201+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Kaitlyn Dianna Weldon",
"item_type": "entity",
"text": "reviewed gene: ARID1A: Rating: GREEN; Mode of pathogenicity: None; Publications: NBK131811; Phenotypes: Coffin-Siris syndrome MONDO:0015452; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "ARID1A",
"entity_type": "gene"
},
{
"created": "2023-11-19T08:01:13.976576+11:00",
"panel_name": "Cardiomyopathy_Paediatric",
"panel_id": 3270,
"panel_version": "0.173",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: RRAGC were changed from Dilated cardiomyopathy (MONDO:0005021), RRAGC-related to Long-Olsen syndrome, MIM# 620609",
"entity_name": "RRAGC",
"entity_type": "gene"
},
{
"created": "2023-11-19T08:00:38.674896+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1376",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: RRAGC were set to 27234373",
"entity_name": "RRAGC",
"entity_type": "gene"
},
{
"created": "2023-11-19T08:00:13.189307+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1375",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: RRAGC were changed from Dilated cardiomyopathy (MONDO:0005021), RRAGC-related to Long-Olsen syndrome, MIM#\t620609",
"entity_name": "RRAGC",
"entity_type": "gene"
},
{
"created": "2023-11-18T21:04:20.311459+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "LUCAS GARCIA ALVES FERREIRA",
"item_type": "entity",
"text": "gene: TXNL4A was added\ngene: TXNL4A was added to Congenital Heart Defect. Sources: Literature\nMode of inheritance for gene: TXNL4A was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: TXNL4A were set to 25434003; 28905882\nPhenotypes for gene: TXNL4A were set to Burn-McKeown syndrome - MIM#608572\nPenetrance for gene: TXNL4A were set to unknown\nReview for gene: TXNL4A was set to AMBER\nAdded comment: Homozygous or compound heterozygous mutation in the TXNL4A gene are associated to Burn-McKeown syndrome (BMKS). BMKS is a rare disorder in which individuals with normal intellectual development exhibit the characteristic combination of choanal atresia, sensorineural deafness, cardiac defects, and typical craniofacial dysmorphism consisting of narrow palpebral fissures, coloboma of the lower eyelids, prominent nose with high nasal bridge, short philtrum, cleft lip and/or palate, and large and protruding ears (Wieczorek et al 2014 - PMID 25434003).\r\n\r\nWieczorek et al (2014 - PMID: 25434003) report 9 families presenting individuals with BMKS and harboring biallelic variants in the TXNL4A gene. Four unrelated individuals presented cardiac defects. \r\n\r\nGoos et al (2017 - PMID: 28905882) report an individual with BMKS including asymptomatic atrial and ventricular septal defects, and harboring biallelic variants in the TXNL4A gene. \nSources: Literature",
"entity_name": "TXNL4A",
"entity_type": "gene"
},
{
"created": "2023-11-17T21:12:24.384875+11:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.5615",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: PBX1 as ready",
"entity_name": "PBX1",
"entity_type": "gene"
},
{
"created": "2023-11-17T21:12:24.358462+11:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.5615",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: pbx1 has been classified as Green List (High Evidence).",
"entity_name": "PBX1",
"entity_type": "gene"
},
{
"created": "2023-11-17T21:12:13.593245+11:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.5615",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: PBX1 were changed from to Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, OMIM #617641",
"entity_name": "PBX1",
"entity_type": "gene"
},
{
"created": "2023-11-17T21:11:36.443060+11:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.5614",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: PBX1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "PBX1",
"entity_type": "gene"
},
{
"created": "2023-11-17T19:35:45.213632+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Laura S",
"item_type": "entity",
"text": "Deleted their comment",
"entity_name": "SMG9",
"entity_type": "gene"
},
{
"created": "2023-11-17T19:35:31.972969+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Laura S",
"item_type": "entity",
"text": "edited their review of gene: SMG9: Added comment: Autosomal recessive inheritance\r\n\r\nShaheen et al. in 2016 (27018474) published case reports about two consanguineous families in which a similar patter of congenital anomalies was found to be most likely caused by homozygous loss-of-function mutation in SMG9. This gene encodes an essential component of the SURF complex that generates phosphor-UPF1, the single most important step in nonsense-mediated decay (NMD). The authors generated a knock-out Smg9 mouse model using CRISPR/Cas9 and observed similar congenital anomaly syndrome to the one reported in humans. Additionally, human cells not expressing SMG9 had global transcriptional dysregulation, but not reduction of premature stop codon (PST)-containing transcripts.\r\n\r\nThe affected family members in these two families showed to have phenotypic overlap between Dandy-Walker malformation and congenital heart disease. Due to the consanguineous nature in both families and the geographical proximity (both cases in Arabia) indicate the possibility of a homozygous pathogenic variants in the same gene. These variants are c.520_521delCC and c.701+4A>G, both affecting the gene SMG9. The indel in family 1 predicts a frameshift and premature truncation, p.Pro174Argfs*12. In family 2, a complete skipping of exon 6 was revealed by RT-PCR. The resulting aberrant transcript predicts frameshift and premature truncation (p.Tyr197Aspfs*10).\r\n\r\nIn 2019, another case was reported by Lecoquierre et al. (31390136). The patient presented with a syndromic association of severe global developmental delay and diverse malformations. She carried a novel SMG9 homozygous variant NM_019108.3:c.1177C>T, p.(Gln393*), while her unaffected parents were both heterozygous and first-degree cousins. This absent variant in gnomaAD was predicted to result in a premature stop codon leading to nonsense-mediated decay within this single transcript gene.\r\n\r\nIn 2020, Lemire et al. (32412169) reported a case of 7-year-old female with severe intellectual disability, multiple congenital anomalies, including cardiovascular anomalies, and facial dysmorphisms. No known consanguinity, the parents were heterozygous for the variant and she had an unaffected brother. She carried a homozygous missense variant in the SMG9 gene (c.1508G > C; p.Trp503Ser) identified as the likely etiology. In silico analysis predicted this change to impact protein structure/function. This missense change is rare, with only one allele count in gnomAD and no homozygotes.\r\n\r\nIn 2021, Altuwaijri et al. (33609422) reported a new case in a research letter to the editor, in which a 25-month-old male had significant heart and brain malformations. Exome sequencing performed on the subject revealed the same homozygous splicing variant (NM_019108.4: exon7:c.701+4A>G) as their original report (Shaheen et al., 2016). Thus validating their previous findings.; Changed publications: 27018474 31390136 32412169 33609422; Changed phenotypes: Heart and brain malformation syndrome (HBMS)",
"entity_name": "SMG9",
"entity_type": "gene"
},
{
"created": "2023-11-17T19:34:29.955662+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Laura S",
"item_type": "entity",
"text": "changed review comment from: Autosomal recessive inheritance\r\n\r\nShaheen et al. in 2016 (27018474) published case reports about two consanguineous families in which a similar patter of congenital anomalies was found to be most likely caused by homozygous loss-of-function mutation in SMG9. This gene encodes an essential component of the SURF complex that generates phosphor-UPF1, the single most important step in nonsense-mediated decay (NMD). The authors generated a knock-out Smg9 mouse model using CRISPR/Cas9 and observed similar congenital anomaly syndrome to the one reported in humans. Additionally, human cells not expressing SMG9 had global transcriptional dysregulation, but not reduction of premature stop codon (PST)-containing transcripts.\r\n\r\nThe affected family members in these two families showed to have phenotypic overlap between Dandy-Walker malformation and congenital heart disease. Due to the consanguineous nature in both families and the geographical proximity (both cases in Arabia) indicate the possibility of a homozygous pathogenic variants in the same gene. These variants are c.520_521delCC and c.701+4A>G, both affecting the gene SMG9. The indel in family 1 predicts a frameshift and premature truncation, p.Pro174Argfs*12. In family 2, a complete skipping of exon 6 was revealed by RT-PCR. The resulting aberrant transcript predicts frameshift and premature truncation (p.Tyr197Aspfs*10).\r\n\r\nIn 2019, another case was reported by Lecoquierre et al. (31390136). The patient presented with a syndromic association of severe global developmental delay and diverse malformations. She carried a novel SMG9 homozygous variant NM_019108.3:c.1177C>T, p.(Gln393*), while her unaffected parents were both heterozygous and first-degree cousins. This absent variant in gnomaAD was predicted to result in a premature stop codon leading to nonsense-mediated decay within this single transcript gene.\r\n\r\nIn 2020, Lemire et al. (32412169) reported a case of 7-year-old female with severe intellectual disability, multiple congenital anomalies, including cardiovascular anomalies, and facial dysmorphisms. No known consanguinity, the parents were heterozygous for the variant and she had an unaffected brother. She carried a homozygous missense variant in the SMG9 gene (c.1508G > C; p.Trp503Ser) identified as the likely etiology. In silico analysis predicted this change to impact protein structure/function. This missense change is rare, with only one allele count in gnomAD and no homozygotes.\r\n\r\nIn 2021, Altuwaijri et al. (33609422) reported a new case in a research letter to the editor, in which a 25-month-old male had significant heart and brain malformations. Exome sequencing performed on the subject revealed the same homozygous splicing variant (NM_019108.4: exon7:c.701+4A>G) as their original report (Shaheen et al., 2016). Thus validating their previous findings. \nSources: Literature; to: Autosomal recessive inheritance\r\n\r\nShaheen et al. in 2016 (27018474) published case reports about two consanguineous families in which a similar patter of congenital anomalies was found to be most likely caused by homozygous loss-of-function mutation in SMG9. This gene encodes an essential component of the SURF complex that generates phosphor-UPF1, the single most important step in nonsense-mediated decay (NMD). The authors generated a knock-out Smg9 mouse model using CRISPR/Cas9 and observed similar congenital anomaly syndrome to the one reported in humans. Additionally, human cells not expressing SMG9 had global transcriptional dysregulation, but not reduction of premature stop codon (PST)-containing transcripts.\r\n\r\nThe affected family members in these two families showed to have phenotypic overlap between Dandy-Walker malformation and congenital heart disease. Due to the consanguineous nature in both families and the geographical proximity (both cases in Arabia) indicate the possibility of a homozygous pathogenic variants in the same gene. These variants are c.520_521delCC and c.701+4A>G, both affecting the gene SMG9. The indel in family 1 predicts a frameshift and premature truncation, p.Pro174Argfs*12. In family 2, a complete skipping of exon 6 was revealed by RT-PCR. The resulting aberrant transcript predicts frameshift and premature truncation (p.Tyr197Aspfs*10).\r\n\r\nIn 2019, another case was reported by Lecoquierre et al. (31390136). The patient presented with a syndromic association of severe global developmental delay and diverse malformations. She carried a novel SMG9 homozygous variant NM_019108.3:c.1177C>T, p.(Gln393*), while her unaffected parents were both heterozygous and first-degree cousins. This absent variant in gnomaAD was predicted to result in a premature stop codon leading to nonsense-mediated decay within this single transcript gene.\r\n\r\nIn 2020, Lemire et al. (32412169) reported a case of 7-year-old female with severe intellectual disability, multiple congenital anomalies, including cardiovascular anomalies, and facial dysmorphisms. No known consanguinity, the parents were heterozygous for the variant and she had an unaffected brother. She carried a homozygous missense variant in the SMG9 gene (c.1508G > C; p.Trp503Ser) identified as the likely etiology. In silico analysis predicted this change to impact protein structure/function. This missense change is rare, with only one allele count in gnomAD and no homozygotes.\r\n\r\nIn 2021, Altuwaijri et al. (33609422) reported a new case in a research letter to the editor, in which a 25-month-old male had significant heart and brain malformations. Exome sequencing performed on the subject revealed the same homozygous splicing variant (NM_019108.4: exon7:c.701+4A>G) as their original report (Shaheen et al., 2016). Thus validating their previous findings. \r\nSources: Literature",
"entity_name": "SMG9",
"entity_type": "gene"
},
{
"created": "2023-11-17T19:33:19.966343+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Laura S",
"item_type": "entity",
"text": "gene: SMG9 was added\ngene: SMG9 was added to Congenital Heart Defect. Sources: Literature\nMode of inheritance for gene: SMG9 was set to Other\nPublications for gene: SMG9 were set to 27018474\nReview for gene: SMG9 was set to RED\nAdded comment: Autosomal recessive inheritance\r\n\r\nShaheen et al. in 2016 (27018474) published case reports about two consanguineous families in which a similar patter of congenital anomalies was found to be most likely caused by homozygous loss-of-function mutation in SMG9. This gene encodes an essential component of the SURF complex that generates phosphor-UPF1, the single most important step in nonsense-mediated decay (NMD). The authors generated a knock-out Smg9 mouse model using CRISPR/Cas9 and observed similar congenital anomaly syndrome to the one reported in humans. Additionally, human cells not expressing SMG9 had global transcriptional dysregulation, but not reduction of premature stop codon (PST)-containing transcripts.\r\n\r\nThe affected family members in these two families showed to have phenotypic overlap between Dandy-Walker malformation and congenital heart disease. Due to the consanguineous nature in both families and the geographical proximity (both cases in Arabia) indicate the possibility of a homozygous pathogenic variants in the same gene. These variants are c.520_521delCC and c.701+4A>G, both affecting the gene SMG9. The indel in family 1 predicts a frameshift and premature truncation, p.Pro174Argfs*12. In family 2, a complete skipping of exon 6 was revealed by RT-PCR. The resulting aberrant transcript predicts frameshift and premature truncation (p.Tyr197Aspfs*10).\r\n\r\nIn 2019, another case was reported by Lecoquierre et al. (31390136). The patient presented with a syndromic association of severe global developmental delay and diverse malformations. She carried a novel SMG9 homozygous variant NM_019108.3:c.1177C>T, p.(Gln393*), while her unaffected parents were both heterozygous and first-degree cousins. This absent variant in gnomaAD was predicted to result in a premature stop codon leading to nonsense-mediated decay within this single transcript gene.\r\n\r\nIn 2020, Lemire et al. (32412169) reported a case of 7-year-old female with severe intellectual disability, multiple congenital anomalies, including cardiovascular anomalies, and facial dysmorphisms. No known consanguinity, the parents were heterozygous for the variant and she had an unaffected brother. She carried a homozygous missense variant in the SMG9 gene (c.1508G > C; p.Trp503Ser) identified as the likely etiology. In silico analysis predicted this change to impact protein structure/function. This missense change is rare, with only one allele count in gnomAD and no homozygotes.\r\n\r\nIn 2021, Altuwaijri et al. (33609422) reported a new case in a research letter to the editor, in which a 25-month-old male had significant heart and brain malformations. Exome sequencing performed on the subject revealed the same homozygous splicing variant (NM_019108.4: exon7:c.701+4A>G) as their original report (Shaheen et al., 2016). Thus validating their previous findings. \nSources: Literature",
"entity_name": "SMG9",
"entity_type": "gene"
},
{
"created": "2023-11-17T09:45:41.022067+11:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.5613",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "reviewed gene: PBX1: Rating: GREEN; Mode of pathogenicity: None; Publications: Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, OMIM #617641; Phenotypes: Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay, OMIM #617641; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes",
"entity_name": "PBX1",
"entity_type": "gene"
},
{
"created": "2023-11-16T17:43:40.237215+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1374",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: SLCO1B3 were set to 33860121",
"entity_name": "SLCO1B3",
"entity_type": "gene"
},
{
"created": "2023-11-16T17:43:17.737749+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1373",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: SLCO1B3 as Green List (high evidence)",
"entity_name": "SLCO1B3",
"entity_type": "gene"
},
{
"created": "2023-11-16T17:43:17.729444+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1373",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: slco1b3 has been classified as Green List (High Evidence).",
"entity_name": "SLCO1B3",
"entity_type": "gene"
},
{
"created": "2023-11-16T17:43:00.350278+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1372",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: SLCO1B3: Added comment: Five additional individuals reported.; Changed rating: GREEN; Changed publications: 33860121, 36964102",
"entity_name": "SLCO1B3",
"entity_type": "gene"
},
{
"created": "2023-11-16T17:42:18.198688+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1372",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: SLCO1B1 were set to 30250148; 24918167; 33860121",
"entity_name": "SLCO1B1",
"entity_type": "gene"
},
{
"created": "2023-11-16T17:41:53.242299+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1371",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: SLCO1B1: Changed publications: 36964102, 33860121",
"entity_name": "SLCO1B1",
"entity_type": "gene"
},
{
"created": "2023-11-16T17:40:54.207176+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1371",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: SLCO1B1 as Green List (high evidence)",
"entity_name": "SLCO1B1",
"entity_type": "gene"
},
{
"created": "2023-11-16T17:40:54.183795+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1371",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: slco1b1 has been classified as Green List (High Evidence).",
"entity_name": "SLCO1B1",
"entity_type": "gene"
},
{
"created": "2023-11-16T17:40:35.580423+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1370",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: SLCO1B1: Changed rating: GREEN",
"entity_name": "SLCO1B1",
"entity_type": "gene"
},
{
"created": "2023-11-16T17:40:24.953684+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1370",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: SLCO1B1: Added comment: Five additional individuals reported.; Changed publications: 33860121, 33860121",
"entity_name": "SLCO1B1",
"entity_type": "gene"
},
{
"created": "2023-11-16T15:06:04.621306+11:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.5613",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: KCNJ11 as Red List (low evidence)",
"entity_name": "KCNJ11",
"entity_type": "gene"
},
{
"created": "2023-11-16T15:06:04.612028+11:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.5613",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: kcnj11 has been classified as Red List (Low Evidence).",
"entity_name": "KCNJ11",
"entity_type": "gene"
},
{
"created": "2023-11-16T15:05:29.207955+11:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.5612",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "reviewed gene: KCNJ11: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None",
"entity_name": "KCNJ11",
"entity_type": "gene"
},
{
"created": "2023-11-16T12:58:10.856215+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: DOCK6 as ready",
"entity_name": "DOCK6",
"entity_type": "gene"
},
{
"created": "2023-11-16T12:58:10.843816+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: dock6 has been classified as Green List (High Evidence).",
"entity_name": "DOCK6",
"entity_type": "gene"
},
{
"created": "2023-11-16T12:57:51.627553+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.315",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: DOCK6 were changed from to Adams-Oliver syndrome 2 MIM#614219",
"entity_name": "DOCK6",
"entity_type": "gene"
},
{
"created": "2023-11-16T12:57:18.802419+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.314",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: DOCK6 were set to ",
"entity_name": "DOCK6",
"entity_type": "gene"
},
{
"created": "2023-11-16T12:56:58.453006+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.314",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: DOCK6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "DOCK6",
"entity_type": "gene"
},
{
"created": "2023-11-16T12:56:27.953473+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.313",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: DOCK6: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "DOCK6",
"entity_type": "gene"
},
{
"created": "2023-11-16T12:56:07.876906+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.313",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: DOCK6: Rating: GREEN; Mode of pathogenicity: None; Publications: 28160419; Phenotypes: Adams-Oliver syndrome 2 MIM#614219; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "DOCK6",
"entity_type": "gene"
},
{
"created": "2023-11-16T08:22:27.551099+11:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.5612",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: KCNA3 were set to ",
"entity_name": "KCNA3",
"entity_type": "gene"
},
{
"created": "2023-11-16T08:21:51.591272+11:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.5611",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: KCNA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37964487; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, KCNA3-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "KCNA3",
"entity_type": "gene"
},
{
"created": "2023-11-16T08:21:13.069083+11:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1947",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: KCNA3 were set to ",
"entity_name": "KCNA3",
"entity_type": "gene"
},
{
"created": "2023-11-16T08:20:29.469488+11:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1946",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: KCNA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37964487; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, KCNA3-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "KCNA3",
"entity_type": "gene"
},
{
"created": "2023-11-16T08:19:55.889484+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1370",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: KCNA3 were set to ",
"entity_name": "KCNA3",
"entity_type": "gene"
},
{
"created": "2023-11-16T08:19:34.663188+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1369",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: KCNA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37964487; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, KCNA3-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "KCNA3",
"entity_type": "gene"
},
{
"created": "2023-11-16T08:06:15.266797+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1369",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: ERG were changed from primary lymphoedema MONDO#0019175, ERG-related to Lymphatic malformation 14, MIM# 620602",
"entity_name": "ERG",
"entity_type": "gene"
},
{
"created": "2023-11-16T08:03:32.310016+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "1.166",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: PLS3 were changed from Bone mineral density QTL18, osteoporosis - MIM#300910; congenital diaphragmatic hernia MONDO:0005711, PLS3-related to Bone mineral density QTL18, osteoporosis - MIM#300910; Diaphragmatic hernia 5, X-linked, MIM# 306950",
"entity_name": "PLS3",
"entity_type": "gene"
},
{
"created": "2023-11-16T08:03:15.033635+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "1.165",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: PLS3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diaphragmatic hernia 5, X-linked, MIM# 306950; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females",
"entity_name": "PLS3",
"entity_type": "gene"
},
{
"created": "2023-11-16T08:02:44.857392+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1368",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: PLS3 were changed from Bone mineral density QTL18, osteoporosis - MIM#300910; congenital diaphragmatic hernia MONDO:0005711, PLS3-related to Bone mineral density QTL18, osteoporosis - MIM#300910; Diaphragmatic hernia 5, X-linked, MIM# 306950",
"entity_name": "PLS3",
"entity_type": "gene"
},
{
"created": "2023-11-16T08:02:08.941568+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1367",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: PLS3: Changed phenotypes: Bone mineral density QTL18, osteoporosis - MIM#300910, Diaphragmatic hernia 5, X-linked, MIM# 306950",
"entity_name": "PLS3",
"entity_type": "gene"
},
{
"created": "2023-11-16T08:01:41.266425+11:00",
"panel_name": "Congenital diaphragmatic hernia",
"panel_id": 69,
"panel_version": "1.14",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: PLS3 were changed from congenital diaphragmatic hernia MONDO:0005711, PLS3-related to Diaphragmatic hernia 5, X-linked, MIM# 306950",
"entity_name": "PLS3",
"entity_type": "gene"
},
{
"created": "2023-11-16T08:01:04.934179+11:00",
"panel_name": "Congenital diaphragmatic hernia",
"panel_id": 69,
"panel_version": "1.13",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: PLS3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diaphragmatic hernia 5, X-linked, MIM# 306950; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females",
"entity_name": "PLS3",
"entity_type": "gene"
},
{
"created": "2023-11-15T21:09:47.666991+11:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.313",
"user_name": "Richard McCoy",
"item_type": "entity",
"text": "reviewed gene: DOCK6: Rating: RED; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 21820096, 23522784, 7606848, 25824905, 25824905, 36789878; Phenotypes: neurological disorders, impaired intellectual development, microcephaly, aplasia cutis congenita, terminal transverse limb defects; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "DOCK6",
"entity_type": "gene"
},
{
"created": "2023-11-15T17:51:14.976094+11:00",
"panel_name": "Bone Marrow Failure",
"panel_id": 56,
"panel_version": "1.59",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: POT1 as ready",
"entity_name": "POT1",
"entity_type": "gene"
},
{
"created": "2023-11-15T17:51:14.962902+11:00",
"panel_name": "Bone Marrow Failure",
"panel_id": 56,
"panel_version": "1.59",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: pot1 has been classified as Green List (High Evidence).",
"entity_name": "POT1",
"entity_type": "gene"
},
{
"created": "2023-11-15T17:51:06.086271+11:00",
"panel_name": "Bone Marrow Failure",
"panel_id": 56,
"panel_version": "1.59",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: POT1 as Green List (high evidence)",
"entity_name": "POT1",
"entity_type": "gene"
},
{
"created": "2023-11-15T17:51:06.075037+11:00",
"panel_name": "Bone Marrow Failure",
"panel_id": 56,
"panel_version": "1.59",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: pot1 has been classified as Green List (High Evidence).",
"entity_name": "POT1",
"entity_type": "gene"
},
{
"created": "2023-11-15T06:24:26.108656+11:00",
"panel_name": "Mitochondrial disease",
"panel_id": 203,
"panel_version": "0.893",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: TOMM7 were changed from Inborn mitochondrial disorder MONDO:0004069, TOMM7-related to Garg-Mishra progeroid syndrome, MIM# 620601",
"entity_name": "TOMM7",
"entity_type": "gene"
}
]
}