{"count":221416,"next":"https://panelapp-aus.org/api/v1/activities/?format=json&page=516","previous":"https://panelapp-aus.org/api/v1/activities/?format=json&page=514","results":[{"created":"2023-11-22T15:31:15.149796+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.358","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: PIGV were changed from mental retardation; seizures and hypotonia; hyperphosphatasia; facial dysmorphism; variable degrees of brachytelephalangy to Hyperphosphatasia with impaired intellectual development syndrome 1, MIM# 239300","entity_name":"PIGV","entity_type":"gene"},{"created":"2023-11-22T15:29:53.885013+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.357","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: PIGV as Amber List (moderate evidence)","entity_name":"PIGV","entity_type":"gene"},{"created":"2023-11-22T15:29:53.872123+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.357","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: pigv has been classified as Amber List (Moderate Evidence).","entity_name":"PIGV","entity_type":"gene"},{"created":"2023-11-22T15:29:21.071627+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.356","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: PIGV: Rating: AMBER; Mode of pathogenicity: None; Publications: 24129430; Phenotypes: Hyperphosphatasia with impaired intellectual development syndrome 1, MIM# 239300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"PIGV","entity_type":"gene"},{"created":"2023-11-22T15:24:34.814332+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.356","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: CRELD1 as ready","entity_name":"CRELD1","entity_type":"gene"},{"created":"2023-11-22T15:24:34.802436+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.356","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: creld1 has been classified as Red List (Low Evidence).","entity_name":"CRELD1","entity_type":"gene"},{"created":"2023-11-22T15:24:29.157110+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.356","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: CRELD1 were changed from  to Atrioventricular septal defect, susceptibility to, 2; Atrioventricular septal defect, partial, with heterotaxy syndrome MIM#606217","entity_name":"CRELD1","entity_type":"gene"},{"created":"2023-11-22T15:23:57.407457+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.355","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: CRELD1 were set to ","entity_name":"CRELD1","entity_type":"gene"},{"created":"2023-11-22T15:23:05.963440+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.354","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: CRELD1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"CRELD1","entity_type":"gene"},{"created":"2023-11-22T15:22:35.553583+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.353","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: CRELD1 as Red List (low evidence)","entity_name":"CRELD1","entity_type":"gene"},{"created":"2023-11-22T15:22:35.543877+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.353","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: creld1 has been classified as Red List (Low Evidence).","entity_name":"CRELD1","entity_type":"gene"},{"created":"2023-11-22T15:21:57.341068+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.352","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: CRELD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Atrioventricular septal defect, susceptibility to, 2, Atrioventricular septal defect, partial, with heterotaxy syndrome MIM#606217; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"CRELD1","entity_type":"gene"},{"created":"2023-11-22T15:19:27.999519+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.352","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: ARID1A as ready","entity_name":"ARID1A","entity_type":"gene"},{"created":"2023-11-22T15:19:27.988774+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.352","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: arid1a has been classified as Green List (High Evidence).","entity_name":"ARID1A","entity_type":"gene"},{"created":"2023-11-22T15:19:25.342626+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.352","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: ARID1A were changed from  to Coffin-Siris syndrome MONDO:0015452","entity_name":"ARID1A","entity_type":"gene"},{"created":"2023-11-22T15:18:53.355384+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.351","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: ARID1A were set to ","entity_name":"ARID1A","entity_type":"gene"},{"created":"2023-11-22T15:18:05.145818+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.350","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: ARID1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"ARID1A","entity_type":"gene"},{"created":"2023-11-22T15:17:11.279713+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.349","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: MAP3K7 as ready","entity_name":"MAP3K7","entity_type":"gene"},{"created":"2023-11-22T15:17:11.261346+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.349","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: map3k7 has been classified as Green List (High Evidence).","entity_name":"MAP3K7","entity_type":"gene"},{"created":"2023-11-22T15:17:06.093212+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.349","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: MAP3K7 as Green List (high evidence)","entity_name":"MAP3K7","entity_type":"gene"},{"created":"2023-11-22T15:17:06.045678+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.349","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: map3k7 has been classified as Green List (High Evidence).","entity_name":"MAP3K7","entity_type":"gene"},{"created":"2023-11-22T15:10:53.432877+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.348","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: NUP188 as ready","entity_name":"NUP188","entity_type":"gene"},{"created":"2023-11-22T15:10:53.422260+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.348","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: nup188 has been classified as Green List (High Evidence).","entity_name":"NUP188","entity_type":"gene"},{"created":"2023-11-22T15:10:47.478028+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.348","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: NUP188 as Green List (high evidence)","entity_name":"NUP188","entity_type":"gene"},{"created":"2023-11-22T15:10:47.453889+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.348","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: nup188 has been classified as Green List (High Evidence).","entity_name":"NUP188","entity_type":"gene"},{"created":"2023-11-22T15:09:35.963503+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.347","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: JAG1 as ready","entity_name":"JAG1","entity_type":"gene"},{"created":"2023-11-22T15:09:35.948217+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.347","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: jag1 has been classified as Green List (High Evidence).","entity_name":"JAG1","entity_type":"gene"},{"created":"2023-11-22T15:09:32.404779+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.347","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: JAG1 were changed from  to Alagille syndrome 1 #118450","entity_name":"JAG1","entity_type":"gene"},{"created":"2023-11-22T15:09:08.335493+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.346","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: JAG1 were set to ","entity_name":"JAG1","entity_type":"gene"},{"created":"2023-11-22T15:08:26.716029+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.345","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: JAG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"JAG1","entity_type":"gene"},{"created":"2023-11-22T15:07:26.376664+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.344","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: GATA6 as ready","entity_name":"GATA6","entity_type":"gene"},{"created":"2023-11-22T15:07:26.353413+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.344","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: gata6 has been classified as Green List (High Evidence).","entity_name":"GATA6","entity_type":"gene"},{"created":"2023-11-22T15:07:20.726563+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.344","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: GATA6 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"GATA6","entity_type":"gene"},{"created":"2023-11-22T15:06:51.029523+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.343","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: GATA6 were set to 22158542; 23223019; 23635550","entity_name":"GATA6","entity_type":"gene"},{"created":"2023-11-22T15:06:19.081398+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.342","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: GATA6 were changed from  to Pancreatic agenesis and congenital heart defects, MIM# 600001","entity_name":"GATA6","entity_type":"gene"},{"created":"2023-11-22T15:05:41.687625+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.341","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: GATA6 were set to ","entity_name":"GATA6","entity_type":"gene"},{"created":"2023-11-22T15:05:10.810558+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.340","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: GATA6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"GATA6","entity_type":"gene"},{"created":"2023-11-22T15:04:16.125774+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.339","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: BRAF as ready","entity_name":"BRAF","entity_type":"gene"},{"created":"2023-11-22T15:04:16.105392+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.339","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: braf has been classified as Green List (High Evidence).","entity_name":"BRAF","entity_type":"gene"},{"created":"2023-11-22T15:04:13.378619+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.339","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: BRAF were changed from  to Cardiofaciocutaneous syndrome, 115150; Noonan syndrome 7, 613706","entity_name":"BRAF","entity_type":"gene"},{"created":"2023-11-22T15:03:41.475383+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.338","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: BRAF were set to ","entity_name":"BRAF","entity_type":"gene"},{"created":"2023-11-22T15:03:09.430254+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.337","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of pathogenicity for gene: BRAF was changed from  to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments","entity_name":"BRAF","entity_type":"gene"},{"created":"2023-11-22T15:02:41.417711+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.336","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: BRAF was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"BRAF","entity_type":"gene"},{"created":"2023-11-22T14:15:03.951237+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.335","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: MED12 as ready","entity_name":"MED12","entity_type":"gene"},{"created":"2023-11-22T14:15:03.935293+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.335","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: med12 has been classified as Green List (High Evidence).","entity_name":"MED12","entity_type":"gene"},{"created":"2023-11-22T14:14:57.613487+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.335","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: MED12 were changed from Dilated cardiomyopathy (DCM); left ventricular non-compaction (LVNC); dilated cardiomyopathy (DCM); arrhythmia; ventricular septal defect (VSD) to Hardikar syndrome, MIM# 301068; Lujan-Fryns syndrome, MIM# 309520; Ohdo syndrome, X-linked, MIM# 300895","entity_name":"MED12","entity_type":"gene"},{"created":"2023-11-22T14:14:18.086983+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.334","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: MED12 as Green List (high evidence)","entity_name":"MED12","entity_type":"gene"},{"created":"2023-11-22T14:14:18.069431+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.334","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: med12 has been classified as Green List (High Evidence).","entity_name":"MED12","entity_type":"gene"},{"created":"2023-11-22T14:13:45.928449+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.333","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: MED12: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hardikar syndrome, MIM# 301068, Lujan-Fryns syndrome, MIM# 309520, Ohdo syndrome, X-linked, MIM# 300895; 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":"2023-11-22T14:11:04.278978+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.333","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: THOC6 as ready","entity_name":"THOC6","entity_type":"gene"},{"created":"2023-11-22T14:11:04.263111+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.333","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: thoc6 has been classified as Green List (High Evidence).","entity_name":"THOC6","entity_type":"gene"},{"created":"2023-11-22T14:10:59.042227+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.333","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: THOC6 were changed from 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 to Beaulieu-Boycott-Innes syndrome (OMIM#613680)","entity_name":"THOC6","entity_type":"gene"},{"created":"2023-11-22T14:10:18.407807+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.332","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: THOC6 as Green List (high evidence)","entity_name":"THOC6","entity_type":"gene"},{"created":"2023-11-22T14:10:18.396982+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.332","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: thoc6 has been classified as Green List (High Evidence).","entity_name":"THOC6","entity_type":"gene"},{"created":"2023-11-22T14:09:44.944758+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.331","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: THOC6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Beaulieu-Boycott-Innes syndrome (OMIM#613680); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"THOC6","entity_type":"gene"},{"created":"2023-11-22T14:03:56.038176+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.331","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: LTBP2 as ready","entity_name":"LTBP2","entity_type":"gene"},{"created":"2023-11-22T14:03:56.019443+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.331","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: ltbp2 has been classified as Red List (Low Evidence).","entity_name":"LTBP2","entity_type":"gene"},{"created":"2023-11-22T14:03:44.372429+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.331","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: LTBP2 were set to 33098376; 35245370; 31512380; 22539340","entity_name":"LTBP2","entity_type":"gene"},{"created":"2023-11-22T14:03:09.995452+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.330","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: LTBP2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal","entity_name":"LTBP2","entity_type":"gene"},{"created":"2023-11-22T14:02:16.476521+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.329","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: LTBP2 as Red List (low evidence)","entity_name":"LTBP2","entity_type":"gene"},{"created":"2023-11-22T14:02:16.461919+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.329","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: ltbp2 has been classified as Red List (Low Evidence).","entity_name":"LTBP2","entity_type":"gene"},{"created":"2023-11-22T14:00:38.765829+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.328","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: LTBP2: Rating: RED; Mode of pathogenicity: None; Publications: 30565850; Phenotypes: Marfan-like disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"LTBP2","entity_type":"gene"},{"created":"2023-11-22T13:55:20.219874+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.328","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: MYBPC3 as ready","entity_name":"MYBPC3","entity_type":"gene"},{"created":"2023-11-22T13:55:20.208322+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.328","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mybpc3 has been classified as Amber List (Moderate Evidence).","entity_name":"MYBPC3","entity_type":"gene"},{"created":"2023-11-22T13:55:13.485007+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.328","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: MYBPC3 were set to 25335496; 16679492","entity_name":"MYBPC3","entity_type":"gene"},{"created":"2023-11-22T13:54:44.799681+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.327","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: MYBPC3 were changed from  to Cardiomyopathy, hypertrophic, 4, MIM# 115197","entity_name":"MYBPC3","entity_type":"gene"},{"created":"2023-11-22T13:54:25.500978+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.327","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: MYBPC3 were set to ","entity_name":"MYBPC3","entity_type":"gene"},{"created":"2023-11-22T13:51:25.940972+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.326","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: MYBPC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal","entity_name":"MYBPC3","entity_type":"gene"},{"created":"2023-11-22T13:50:57.909451+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.325","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: MYBPC3 as Amber List (moderate evidence)","entity_name":"MYBPC3","entity_type":"gene"},{"created":"2023-11-22T13:50:57.899534+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.325","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: mybpc3 has been classified as Amber List (Moderate Evidence).","entity_name":"MYBPC3","entity_type":"gene"},{"created":"2023-11-22T13:50:25.621733+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.324","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: MYBPC3: Rating: AMBER; Mode of pathogenicity: None; Publications: 25335496, 16679492; Phenotypes: Cardiomyopathy, hypertrophic, 4, MIM# 115197; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"MYBPC3","entity_type":"gene"},{"created":"2023-11-22T13:45:43.869096+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.324","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: PKD1L1 as ready","entity_name":"PKD1L1","entity_type":"gene"},{"created":"2023-11-22T13:45:43.859424+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.324","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: pkd1l1 has been classified as Green List (High Evidence).","entity_name":"PKD1L1","entity_type":"gene"},{"created":"2023-11-22T13:45:35.577870+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.324","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: PKD1L1 as Green List (high evidence)","entity_name":"PKD1L1","entity_type":"gene"},{"created":"2023-11-22T13:45:35.561039+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.324","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: pkd1l1 has been classified as Green List (High Evidence).","entity_name":"PKD1L1","entity_type":"gene"},{"created":"2023-11-22T13:44:05.361939+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.323","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: ARID1B as ready","entity_name":"ARID1B","entity_type":"gene"},{"created":"2023-11-22T13:44:05.352699+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.323","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: arid1b has been classified as Green List (High Evidence).","entity_name":"ARID1B","entity_type":"gene"},{"created":"2023-11-22T13:43:59.216540+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.323","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: ARID1B were set to 35579625; 35445787; 29549119; 34324492","entity_name":"ARID1B","entity_type":"gene"},{"created":"2023-11-22T13:43:28.178128+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.322","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: ARID1B were changed from  to Coffin-Siris syndrome 1, MIM# 135900","entity_name":"ARID1B","entity_type":"gene"},{"created":"2023-11-22T13:42:47.094849+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.321","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: ARID1B were set to ","entity_name":"ARID1B","entity_type":"gene"},{"created":"2023-11-22T13:41:47.551033+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.320","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: ARID1B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"ARID1B","entity_type":"gene"},{"created":"2023-11-22T13:40:45.736635+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.319","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: KMT2B as ready","entity_name":"KMT2B","entity_type":"gene"},{"created":"2023-11-22T13:40:45.722670+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.319","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: kmt2b has been classified as Red List (Low Evidence).","entity_name":"KMT2B","entity_type":"gene"},{"created":"2023-11-22T13:40:42.315890+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.319","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: KMT2B were changed from  to Dystonia 28,Childhood-onset; DYT28(617284); Intellectual Developmental disorder, Autosomal dominant; MRD68(619934)","entity_name":"KMT2B","entity_type":"gene"},{"created":"2023-11-22T13:40:11.533146+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.318","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: KMT2B were set to ","entity_name":"KMT2B","entity_type":"gene"},{"created":"2023-11-22T13:39:39.583634+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.317","user_name":"Zornitza Stark","item_type":"entity","text":"Mode of inheritance for gene: KMT2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"KMT2B","entity_type":"gene"},{"created":"2023-11-22T13:36:08.570214+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.316","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: KMT2B as Red List (low evidence)","entity_name":"KMT2B","entity_type":"gene"},{"created":"2023-11-22T13:36:08.550444+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.316","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: kmt2b has been classified as Red List (Low Evidence).","entity_name":"KMT2B","entity_type":"gene"},{"created":"2023-11-22T13:35:38.114301+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.315","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: KMT2B: Rating: RED; Mode of pathogenicity: None; Publications: 33150406; Phenotypes: Dystonia 28,Childhood-onset, DYT28(617284), Intellectual Developmental disorder, Autosomal dominant, MRD68(619934); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"KMT2B","entity_type":"gene"},{"created":"2023-11-22T11:58:11.595212+11:00","panel_name":"Incidentalome","panel_id":126,"panel_version":"0.295","user_name":"Zornitza Stark","item_type":"entity","text":"commented on gene: CCNF: LIMITED by ClinGen","entity_name":"CCNF","entity_type":"gene"},{"created":"2023-11-22T11:57:45.858595+11:00","panel_name":"Incidentalome","panel_id":126,"panel_version":"0.295","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: CCNF: Changed rating: AMBER","entity_name":"CCNF","entity_type":"gene"},{"created":"2023-11-22T11:57:27.261514+11:00","panel_name":"Motor Neurone Disease","panel_id":25,"panel_version":"1.8","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: CCNF: Changed rating: AMBER","entity_name":"CCNF","entity_type":"gene"},{"created":"2023-11-22T11:57:07.429760+11:00","panel_name":"Early-onset Dementia","panel_id":24,"panel_version":"1.5","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: CCNF: Changed rating: AMBER","entity_name":"CCNF","entity_type":"gene"},{"created":"2023-11-22T06:46:28.079821+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.315","user_name":"Violeta Velkoska-Ivanova","item_type":"entity","text":"changed review comment from: There is insufficient evidence in the published data to rate this gene as green in the context of congenital heart disease. The supporting evidence for rating this gene AMBER is as follows:\r\n No heart abnormalities were noted in the synopsis of the two KMT2B-associated disease phenotypes listed in OMIM ( both reviewed in 2022). \r\n   The GenCC database( https://thegencc.org/) has summarised evidence from four reputable submitters: Genomic England Panel App, ClinGen, Ambry Genetics and Orphanet). Three classifications (two supportive, one strong) implicate KMT2B in two diseases: Dystonia,28, childhood-onset (MONDO:0015004; OMIM: 617284) and Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516) where the KMT2B variations are inherited in autosomal dominant mode.\r\n       The ClinGen evaluation (The Clinical Genome Resource), with ten variants (missense, nonsense, and frameshift) being reported in 10 probands in 2 publications (PMIDs: 29276005, 33150406) and also in a non-human animal model (PMID: 23426673) provides definitive evidence for the KMT2B gene relationship with autosomal dominant, Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516). Regarding dosage sensitivity, there is sufficient evidence that this gene exhibits haploinsufficiency and is intolerant to LoF variation.  \r\nThe G2P database (https://www.ebi.ac.uk/gene2phenotype/) lists the KMT2B-associated complex early-onset dystonia in the Developmental Delay panel. Also, the KMT2B is absent from the Cardiac G2P, a publicly available resource designed for filtering and analysing genetic variants of inherited cardiac conditions (ICC)(PMID 37872640). \r\n     The largest cohort with KMT2B variants (133 patients: 53 as the initial study cohort in addition to 80 published cases)(PMID:33150406) provides a detailed delineation of their clinical phenotype and molecular genetic features. Although this study emphasised that patients with chromosomal deletions and protein-truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants, it reported on new disease features ( i.e. atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype). It also identified co-morbidities ( i.e. risk of status dystonicus, intrauterine growth retardation, and endocrinopathies); however, it failed to associate the KMT2B gene with congenital abnormalities of the heart.; to: There is insufficient evidence in the published data to rate this gene as green in the context of congenital heart disease. The supporting evidence for rating this gene AMBER is as follows:\r\n No heart abnormalities were noted in the two KMT2B-associated disease phenotypes listed in OMIM ( both reviewed in 2022).\r\n   The GenCC database( https://thegencc.org/) has summarised evidence from four reputable submitters: Genomic England Panel App, ClinGen, Ambry Genetics and Orphanet). Three classifications (two supportive, one strong) implicate KMT2B in two diseases: Dystonia,28, childhood-onset (MONDO:0015004; OMIM: 617284) and Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516) where the KMT2B variations are inherited in autosomal dominant mode.\r\n       The ClinGen evaluation (The Clinical Genome Resource), with ten variants (missense, nonsense, and frameshift) being reported in 10 probands in 2 publications (PMIDs: 29276005, 33150406) and also in a non-human animal model (PMID: 23426673) provides definitive evidence for the KMT2B gene relationship with autosomal dominant, Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516). Regarding dosage sensitivity, there is sufficient evidence that this gene exhibits haploinsufficiency and is intolerant to LoF variation.  \r\nThe G2P database (https://www.ebi.ac.uk/gene2phenotype/) lists the KMT2B-associated complex early-onset dystonia in the Developmental Delay panel. Also, the KMT2B is absent from the Cardiac G2P, a publicly available resource designed for filtering and analysing genetic variants of inherited cardiac conditions (ICC)(PMID 37872640). \r\n     The largest cohort with KMT2B variants (133 patients: 53 as the initial study cohort in addition to 80 published cases)(PMID:33150406) provides a detailed delineation of their clinical phenotype and molecular genetic features. Although this study emphasised that patients with chromosomal deletions and protein-truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants, it reported on new disease features ( i.e. atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype). It also identified co-morbidities ( i.e. risk of status dystonicus, intrauterine growth retardation, and endocrinopathies); however, it failed to associate the KMT2B gene with congenital abnormalities of the heart.\r\n","entity_name":"KMT2B","entity_type":"gene"},{"created":"2023-11-22T06:04:57.519410+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.315","user_name":"Violeta Velkoska-Ivanova","item_type":"entity","text":"changed review comment from: There is insufficient evidence in the published data to rate this gene as green in the context of congenital heart disease. The supporting evidence for rating this gene AMBER is as follows:\r\n No heart abnormalities were noted in the synopsis of the two KMT2B-associated disease phenotypes listed in OMIM ( both reviewed in 2022). \r\n   The GenCC database( https://thegencc.org/) has summarised evidence from four reputable submitters: Genomic England Panel App, ClinGen, Ambry Genetics and Orphanet). Three classifications (two supportive, one strong) implicate KMT2B in two diseases: Dystonia,28, childhood-onset (MONDO:0015004; OMIM: 617284) and Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516) where the KMT2B variations are inherited in autosomal dominant mode.\r\n       The ClinGen evaluation (The Clinical Genome Resource), with ten variants (missense, nonsense, and frameshift) being reported in 10 probands in 2 publications (PMIDs: 29276005, 33150406) and also in a non-human animal model (PMID: 23426673) provides definitive evidence for the KMT2B gene relationship with autosomal dominant, Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516). Regarding dosage sensitivity, there is sufficient evidence that this gene exhibits haploinsufficiency and is intolerant to LoF variation.  \r\nThe G2P database (https://www.ebi.ac.uk/gene2phenotype/) only enlists the KMT2B gene in the Developmental Delay panel. The KMT2B is absent from the Cardiac G2P, a publicly available resource designed to aid in the filtering and analysing genetic variants of inherited cardiac conditions (ICC)(PMID 37872640). \r\n     The largest cohort with KMT2B variants (133 patients: 53 as the initial study cohort in addition to 80 published cases)(PMID:33150406) provides a detailed delineation of their clinical phenotype and molecular genetic features. Although this study emphasised that patients with chromosomal deletions and protein-truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants, it reported on new disease features ( i.e. atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype). It also identified co-morbidities ( i.e. risk of status dystonicus, intrauterine growth retardation, and endocrinopathies); however, it failed to associate the KMT2B gene with congenital abnormalities of the heart.; to: There is insufficient evidence in the published data to rate this gene as green in the context of congenital heart disease. The supporting evidence for rating this gene AMBER is as follows:\r\n No heart abnormalities were noted in the synopsis of the two KMT2B-associated disease phenotypes listed in OMIM ( both reviewed in 2022). \r\n   The GenCC database( https://thegencc.org/) has summarised evidence from four reputable submitters: Genomic England Panel App, ClinGen, Ambry Genetics and Orphanet). Three classifications (two supportive, one strong) implicate KMT2B in two diseases: Dystonia,28, childhood-onset (MONDO:0015004; OMIM: 617284) and Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516) where the KMT2B variations are inherited in autosomal dominant mode.\r\n       The ClinGen evaluation (The Clinical Genome Resource), with ten variants (missense, nonsense, and frameshift) being reported in 10 probands in 2 publications (PMIDs: 29276005, 33150406) and also in a non-human animal model (PMID: 23426673) provides definitive evidence for the KMT2B gene relationship with autosomal dominant, Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516). Regarding dosage sensitivity, there is sufficient evidence that this gene exhibits haploinsufficiency and is intolerant to LoF variation.  \r\nThe G2P database (https://www.ebi.ac.uk/gene2phenotype/) lists the KMT2B-associated complex early-onset dystonia in the Developmental Delay panel. Also, the KMT2B is absent from the Cardiac G2P, a publicly available resource designed for filtering and analysing genetic variants of inherited cardiac conditions (ICC)(PMID 37872640). \r\n     The largest cohort with KMT2B variants (133 patients: 53 as the initial study cohort in addition to 80 published cases)(PMID:33150406) provides a detailed delineation of their clinical phenotype and molecular genetic features. Although this study emphasised that patients with chromosomal deletions and protein-truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants, it reported on new disease features ( i.e. atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype). It also identified co-morbidities ( i.e. risk of status dystonicus, intrauterine growth retardation, and endocrinopathies); however, it failed to associate the KMT2B gene with congenital abnormalities of the heart.","entity_name":"KMT2B","entity_type":"gene"},{"created":"2023-11-22T03:58:15.161026+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.315","user_name":"Violeta Velkoska-Ivanova","item_type":"entity","text":"changed review comment from: There is insufficient evidence in the published data to rate this gene as green in the context of congenital heart disease. \r\nThe Gene Cards summary emphasises the \r\n   The supporting evidence for rating this gene AMBER is as follows:\r\n No heart abnormalities have been noted in the synopsis of two phenotypes listed in OMIM ( both reviewed in the year 2022). \r\n   The GenCC database( https://thegencc.org/) has summarised evidence from four reputable submitters: Genomic England Panel App, ClinGen, Ambry Genetics and Orphanet). Three classifications (two supportive, one strong) implicate KMT2B in two diseases: Dystonia,28, childhood-onset (MONDO:0015004; OMIM: 617284) and Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516) where the KMT2B variations are inherited in autosomal dominant mode.\r\n       The KMT2B gene has been evaluated in ClinGen (The Clinical Genome Resource), with ten variants (missense, nonsense, and frameshift) being reported in 10 probands in 2 publications (PMIDs: 29276005, 33150406) and also in a non-human animal model (PMID: 23426673) providing definitive evidence for the KMT2B gene relationship with autosomal dominant, Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516).In terms of dosage sensitivity, there is sufficient evidence this gene exhibits haploinsufficiency and is intolerant to LoF variation.  \r\nThe G2P database (https://www.ebi.ac.uk/gene2phenotype/) only enlists the KMT2B gene in the Developmental Delay panel. The KMT2B is absent from the Cardiac G2P, a publicly available resource designed to aid in the filtering and analysing genetic variants of inherited cardiac conditions (ICC)(PMID 37872640). \r\n     The largest cohort with KMT2B variants (133 patients: 53 as the initial study cohort in addition to 80 published cases)(PMID:33150406) provides a detailed delineation of their clinical phenotype and molecular genetic features. Although this study emphasised that patients with chromosomal deletions and protein-truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants, it reported on new disease features ( i.e. atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype). It also identified co-morbidities ( i.e. risk of status dystonicus, intrauterine growth retardation, and endocrinopathies); however, it failed to associate the KMT2B gene with congenital abnormalities of the heart.; to: There is insufficient evidence in the published data to rate this gene as green in the context of congenital heart disease. The supporting evidence for rating this gene AMBER is as follows:\r\n No heart abnormalities were noted in the synopsis of the two KMT2B-associated disease phenotypes listed in OMIM ( both reviewed in 2022). \r\n   The GenCC database( https://thegencc.org/) has summarised evidence from four reputable submitters: Genomic England Panel App, ClinGen, Ambry Genetics and Orphanet). Three classifications (two supportive, one strong) implicate KMT2B in two diseases: Dystonia,28, childhood-onset (MONDO:0015004; OMIM: 617284) and Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516) where the KMT2B variations are inherited in autosomal dominant mode.\r\n       The ClinGen evaluation (The Clinical Genome Resource), with ten variants (missense, nonsense, and frameshift) being reported in 10 probands in 2 publications (PMIDs: 29276005, 33150406) and also in a non-human animal model (PMID: 23426673) provides definitive evidence for the KMT2B gene relationship with autosomal dominant, Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516). Regarding dosage sensitivity, there is sufficient evidence that this gene exhibits haploinsufficiency and is intolerant to LoF variation.  \r\nThe G2P database (https://www.ebi.ac.uk/gene2phenotype/) only enlists the KMT2B gene in the Developmental Delay panel. The KMT2B is absent from the Cardiac G2P, a publicly available resource designed to aid in the filtering and analysing genetic variants of inherited cardiac conditions (ICC)(PMID 37872640). \r\n     The largest cohort with KMT2B variants (133 patients: 53 as the initial study cohort in addition to 80 published cases)(PMID:33150406) provides a detailed delineation of their clinical phenotype and molecular genetic features. Although this study emphasised that patients with chromosomal deletions and protein-truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants, it reported on new disease features ( i.e. atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype). It also identified co-morbidities ( i.e. risk of status dystonicus, intrauterine growth retardation, and endocrinopathies); however, it failed to associate the KMT2B gene with congenital abnormalities of the heart.","entity_name":"KMT2B","entity_type":"gene"},{"created":"2023-11-22T03:51:34.607948+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.315","user_name":"Violeta Velkoska-Ivanova","item_type":"entity","text":"edited their review of gene: KMT2B: Changed publications: PMID:29276005, 23426673, 33150406, 23665959, 37504561, 28902362, 21646717; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown","entity_name":"KMT2B","entity_type":"gene"},{"created":"2023-11-22T03:40:42.843827+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.315","user_name":"Violeta Velkoska-Ivanova","item_type":"entity","text":"changed review comment from: There is insufficient evidence to rate this gene as green in the context of congenital heart disease. However, this gene is enlisted as Green in PanelApp England in the Fetal Anomalies Panel( v?????)\r\n   The supporting evidence for rating this gene AMBER is as follows:\r\n No heart abnormalities have been noted in the synopsis of two phenotypes listed in OMIM ( both reviewed in the year 2022). \r\n   The GenCC database ( https://thegencc.org/) has summarised evidence from four reputable submitters: Genomic England Panel App, ClinGen, Ambry Genetics and Orphanet). Three classifications (two supportive, one strong) implicate KMT2B in two diseases: Dystonia,28, childhood-onset (MONDO:0015004; OMIM: 617284) and Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516) where the KMT2B variations are inherited in autosomal dominant mode.\r\n       The KMT2B gene has been evaluated in ClinGen (The Clinical Genome Resource), with ten variants (missense, nonsense, and frameshift) being reported in 10 probands in 2 publications (PMIDs: 29276005, 33150406) and also in a non-human animal model (PMID: 23426673) providing definitive evidence for the KMT2B gene relationship with autosomal dominant, Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516).In terms of dosage sensitivity, there is sufficient evidence this gene exhibits haploinsufficiency and is intolerant to LoF variation.  \r\nThe G2P database (https://www.ebi.ac.uk/gene2phenotype/) only enlists the KMT2B gene in the Developmental Delay panel. The KMT2B is absent from the recently published publicly available resource, Cardiac G2P, which is designed to aid in the filtering and analysing of genetic variants of inherited cardiac conditions (ICC)(PMID 37872640). \r\n     The largest cohort with KMT2B variants (133 patients: 53 as the initial study cohort in addition to 80 published cases)(PMID:33150406) provides a detailed delineation of their clinical phenotype and molecular genetic features. Although this study emphasised that patients with chromosomal deletions and protein-truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants, it reported on new disease features ( i.e. atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype). It also identified co-morbidities ( i.e. risk of status dystonicus, intrauterine growth retardation, and endocrinopathies); however, it failed to associate the KMT2B gene with congenital abnormalities of the heart.; to: There is insufficient evidence in the published data to rate this gene as green in the context of congenital heart disease. \r\nThe Gene Cards summary emphasises the \r\n   The supporting evidence for rating this gene AMBER is as follows:\r\n No heart abnormalities have been noted in the synopsis of two phenotypes listed in OMIM ( both reviewed in the year 2022). \r\n   The GenCC database( https://thegencc.org/) has summarised evidence from four reputable submitters: Genomic England Panel App, ClinGen, Ambry Genetics and Orphanet). Three classifications (two supportive, one strong) implicate KMT2B in two diseases: Dystonia,28, childhood-onset (MONDO:0015004; OMIM: 617284) and Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516) where the KMT2B variations are inherited in autosomal dominant mode.\r\n       The KMT2B gene has been evaluated in ClinGen (The Clinical Genome Resource), with ten variants (missense, nonsense, and frameshift) being reported in 10 probands in 2 publications (PMIDs: 29276005, 33150406) and also in a non-human animal model (PMID: 23426673) providing definitive evidence for the KMT2B gene relationship with autosomal dominant, Complex Neurodevelopmental Disorder with Motor features (MONDO: 0100516).In terms of dosage sensitivity, there is sufficient evidence this gene exhibits haploinsufficiency and is intolerant to LoF variation.  \r\nThe G2P database (https://www.ebi.ac.uk/gene2phenotype/) only enlists the KMT2B gene in the Developmental Delay panel. The KMT2B is absent from the Cardiac G2P, a publicly available resource designed to aid in the filtering and analysing genetic variants of inherited cardiac conditions (ICC)(PMID 37872640). \r\n     The largest cohort with KMT2B variants (133 patients: 53 as the initial study cohort in addition to 80 published cases)(PMID:33150406) provides a detailed delineation of their clinical phenotype and molecular genetic features. Although this study emphasised that patients with chromosomal deletions and protein-truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants, it reported on new disease features ( i.e. atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype). It also identified co-morbidities ( i.e. risk of status dystonicus, intrauterine growth retardation, and endocrinopathies); however, it failed to associate the KMT2B gene with congenital abnormalities of the heart.","entity_name":"KMT2B","entity_type":"gene"},{"created":"2023-11-21T18:35:24.681145+11:00","panel_name":"Congenital Heart Defect","panel_id":76,"panel_version":"0.315","user_name":"Violeta Velkoska-Ivanova","item_type":"entity","text":"reviewed gene: KMT2B: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID:29276005, 23426673, 33150406; Phenotypes: Dystonia 28,Childhood-onset, DYT28(617284), Intellectual Developmental disorder, Autosomal dominant, MRD68(619934); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal","entity_name":"KMT2B","entity_type":"gene"},{"created":"2023-11-21T16:32:40.961391+11:00","panel_name":"Disorders of immune dysregulation","panel_id":229,"panel_version":"0.183","user_name":"Peter McNaughton","item_type":"entity","text":"gene: MADD was added\ngene: MADD was added to Disorders of immune dysregulation. Sources: Literature\nMode of inheritance for gene: MADD was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: MADD were set to PMID: 36206192\nPhenotypes for gene: MADD were set to HLH, enteropathy\nReview for gene: MADD was set to AMBER\nAdded comment: 2-month-old female infant born to consanguineous parents was admitted with complex syndromic features of dystrophy, endocrinological dysfunction, and developmental delay developed partial features of HLH with a postnatally acquired cytomegalovirus infection and a persistent secretory enteropathy.  Her brother with similar symptoms had died at 2 years of life.  Severe degranulation defect of resting and IL-2–stimulated NK and cytotoxic T lymphocytes (CTLs) was detected.  MADD knockout cell line showed same defect.\r\nAnother patient displayed reduced degranulation of cytotoxic cells (patient 2 PMID: 32761064) \nSources: Literature","entity_name":"MADD","entity_type":"gene"}]}