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| Early onset or syndromic epilepsy v4.171 | KCNA1 |
Achchuthan Shanmugasundram changed review comment from: PMID:30055040 reported the identification of three heterozygous de novo variants (p.Pro403Ser, p.Pro405Leu, and p.Pro405Ser) in the pore region found in four patients from three families with severe developmental and epileptic encephalopathy (DEE). PMID:34778950 reported the comparison of these variants with a de novo variant in the voltage sensor (p.Ala261Ter) that was identified in two patients with mild, carbamazepine-responsive, focal epilepsy. PMID:32316562 reported from the analyses of 47 deleterious KCNA1 variants that were identified from previous literature and genetic archives that epilepsy or seizure-related variants tend to cluster in the S1,S2,S5,S6 transmembrane domains and in the pore domain. PMID:31586945 reported the identification of a homozygous KCNA1 variant (p.Val368Leu) in a patient presenting with a severe combination of dyskinesia and neonatal epileptic encephalopathy. This variant involves a conserved residue in the pore domain, close to the selectivity signature sequence for K+ ions (TVGYG). Monoallelic variants in this gene have only been associated with episodic ataxia/ myokymia syndrome (MIM #160120) in OMIM, but not with epilepsy/ epileptic encephalopathy, and biallelic variants are not reported with any phenotypes in OMIM. Both monoallelic and biallelic variants have been associated with KCNA1-related epileptic encephalopathy in Gene2Phenotype (with 'limited' rating in the DD panel for both MOIs).; to: PMID:30055040 reported the identification of three heterozygous de novo variants (p.Pro403Ser, p.Pro405Leu, and p.Pro405Ser) in the pore region found in four patients from three families with severe developmental and epileptic encephalopathy (DEE). PMID:34778950 reported the comparison of the three variants from PMID:30055040 with a de novo variant in the voltage sensor (p.Ala261Ter) that was identified in two patients with mild, carbamazepine-responsive, focal epilepsy. PMID:32316562 reported from the analyses of 47 deleterious KCNA1 variants that were identified from previous literature and genetic archives that epilepsy or seizure-related variants tend to cluster in the S1,S2,S5,S6 transmembrane domains and in the pore domain. PMID:31586945 reported the identification of a homozygous KCNA1 variant (p.Val368Leu) in a patient presenting with a severe combination of dyskinesia and neonatal epileptic encephalopathy. This variant involves a conserved residue in the pore domain, close to the selectivity signature sequence for K+ ions (TVGYG). Monoallelic variants in this gene have only been associated with episodic ataxia/ myokymia syndrome (MIM #160120) in OMIM, but not with epilepsy/ epileptic encephalopathy, and biallelic variants are not reported with any phenotypes in OMIM. Both monoallelic and biallelic variants have been associated with KCNA1-related epileptic encephalopathy in Gene2Phenotype (with 'limited' rating in the DD panel for both MOIs). |
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| Early onset or syndromic epilepsy v4.171 | KCNA1 |
Achchuthan Shanmugasundram changed review comment from: PMID:32316562 reported from the analyses of 47 deleterious KCNA1 variants that were identified from previous literature and genetic archives that epilepsy or seizure-related variants tend to cluster in the S1,S2,S5,S6 transmembrane domains and in the pore domain. PMID:34778950 reported the identification of three heterozygous de novo variants (p.Pro403Ser, p.Pro405Leu, and p.Pro405Ser) in the pore region found in four patients from three families with severe developmental and epileptic encephalopathy (DEE) and a de novo variant in the voltage sensor (p.Ala261Ter) identified in two patients with mild, carbamazepine-responsive, focal epilepsy. PMID:31586945 reported the identification of a homozygous KCNA1 variant (p.Val368Leu) in a patient presenting with a severe combination of dyskinesia and neonatal epileptic encephalopathy. This variant involves a conserved residue in the pore domain, close to the selectivity signature sequence for K+ ions (TVGYG). Monoallelic variants in this gene have only been associated with episodic ataxia/ myokymia syndrome (MIM #160120) in OMIM, but not with epilepsy/ epileptic encephalopathy, and biallelic variants are not reported with any phenotypes in OMIM. Both monoallelic and biallelic variants have been associated with KCNA1-related epileptic encephalopathy in Gene2Phenotype (with 'limited' rating in the DD panel for both MOIs).; to: PMID:30055040 reported the identification of three heterozygous de novo variants (p.Pro403Ser, p.Pro405Leu, and p.Pro405Ser) in the pore region found in four patients from three families with severe developmental and epileptic encephalopathy (DEE). PMID:34778950 reported the comparison of these variants with a de novo variant in the voltage sensor (p.Ala261Ter) that was identified in two patients with mild, carbamazepine-responsive, focal epilepsy. PMID:32316562 reported from the analyses of 47 deleterious KCNA1 variants that were identified from previous literature and genetic archives that epilepsy or seizure-related variants tend to cluster in the S1,S2,S5,S6 transmembrane domains and in the pore domain. PMID:31586945 reported the identification of a homozygous KCNA1 variant (p.Val368Leu) in a patient presenting with a severe combination of dyskinesia and neonatal epileptic encephalopathy. This variant involves a conserved residue in the pore domain, close to the selectivity signature sequence for K+ ions (TVGYG). Monoallelic variants in this gene have only been associated with episodic ataxia/ myokymia syndrome (MIM #160120) in OMIM, but not with epilepsy/ epileptic encephalopathy, and biallelic variants are not reported with any phenotypes in OMIM. Both monoallelic and biallelic variants have been associated with KCNA1-related epileptic encephalopathy in Gene2Phenotype (with 'limited' rating in the DD panel for both MOIs). |
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| Early onset or syndromic epilepsy v4.171 | KCNA1 | Achchuthan Shanmugasundram Classified gene: KCNA1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.171 | KCNA1 | Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of monoallelic KCNA1 variants with epilepsy/ epileptic encephalopathy and hence this gene can be promoted to green rating in the next GMS review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.171 | KCNA1 | Achchuthan Shanmugasundram Gene: kcna1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.170 | KCNA1 | Achchuthan Shanmugasundram Publications for gene: KCNA1 were set to 29056246; 11026449; 9581771; 24578548; 31586945; 32316562; 34778950 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.169 | KCNA1 | Achchuthan Shanmugasundram edited their review of gene: KCNA1: Changed publications to: 30055040, 31586945, 32316562, 34778950 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.169 | KCNA1 |
Achchuthan Shanmugasundram changed review comment from: PMID:32316562 reported from the analyses of 47 deleterious KCNA1 variants that were identified from previous literature and genetic archives that epilepsy or seizure-related variants tend to cluster in the S1,S2,S5,S6 transmembrane domains and in the pore domain. PMID:34778950 reported the identification of three heterozygous de novo variants (p.Pro403Ser, p.Pro405Leu, and p.Pro405Ser) in the pore region found in four patients with severe developmental and epileptic encephalopathy (DEE) and a de novo variant in the voltage sensor (p.Ala261Ter) identified in two patients with mild, carbamazepine-responsive, focal epilepsy. PMID:31586945 reported the identification of a homozygous KCNA1 variant (p.Val368Leu) in a patient presenting with a severe combination of dyskinesia and neonatal epileptic encephalopathy. This variant involves a conserved residue in the pore domain, close to the selectivity signature sequence for K+ ions (TVGYG). Monoallelic variants in this gene have only been associated with episodic ataxia/ myokymia syndrome (MIM #160120) in OMIM, but not with epilepsy/ epileptic encephalopathy, and biallelic variants are not reported with any phenotypes in OMIM. Both monoallelic and biallelic variants have been associated with KCNA1-related epileptic encephalopathy in Gene2Phenotype (with 'limited' rating in the DD panel for both MOIs).; to: PMID:32316562 reported from the analyses of 47 deleterious KCNA1 variants that were identified from previous literature and genetic archives that epilepsy or seizure-related variants tend to cluster in the S1,S2,S5,S6 transmembrane domains and in the pore domain. PMID:34778950 reported the identification of three heterozygous de novo variants (p.Pro403Ser, p.Pro405Leu, and p.Pro405Ser) in the pore region found in four patients from three families with severe developmental and epileptic encephalopathy (DEE) and a de novo variant in the voltage sensor (p.Ala261Ter) identified in two patients with mild, carbamazepine-responsive, focal epilepsy. PMID:31586945 reported the identification of a homozygous KCNA1 variant (p.Val368Leu) in a patient presenting with a severe combination of dyskinesia and neonatal epileptic encephalopathy. This variant involves a conserved residue in the pore domain, close to the selectivity signature sequence for K+ ions (TVGYG). Monoallelic variants in this gene have only been associated with episodic ataxia/ myokymia syndrome (MIM #160120) in OMIM, but not with epilepsy/ epileptic encephalopathy, and biallelic variants are not reported with any phenotypes in OMIM. Both monoallelic and biallelic variants have been associated with KCNA1-related epileptic encephalopathy in Gene2Phenotype (with 'limited' rating in the DD panel for both MOIs). |
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| Early onset or syndromic epilepsy v4.169 | KCNA1 | Achchuthan Shanmugasundram Phenotypes for gene: KCNA1 were changed from Episodic ataxia/myokymia syndrome 160120 to Episodic ataxia/ myokymia syndrome, OMIM:160120; epilepsy, MONDO:0005027 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.168 | KCNA1 | Achchuthan Shanmugasundram Publications for gene: KCNA1 were set to 29056246; 11026449; 9581771; 24578548 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.167 | KCNA1 | Achchuthan Shanmugasundram Mode of inheritance for gene: KCNA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.166 | KCNA1 |
Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: KCNA1. Tag Q1_24_NHS_review tag was added to gene: KCNA1. |
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| Early onset or syndromic epilepsy v4.166 | KCNA1 | Achchuthan Shanmugasundram reviewed gene: KCNA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31586945, 32316562, 34778950; Phenotypes: epilepsy, MONDO:0005027; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.164 | KCNA1 | Tracy Lester Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.164 | KCNA1 | Tracy Lester edited their review of gene: KCNA1: Added comment: There have been several recent reports that show de novo missense variants in specific regions of this gene are associated with epileptic encephalopathy, supported by functional studies, and gene now meets criteria to be green for this phenotype; Changed rating: GREEN; Changed publications to: 24578548, 3055040, 34778950; Changed phenotypes to: epilep | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.435 | KCNA1 | Rebecca Foulger Classified gene: KCNA1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.435 | KCNA1 | Rebecca Foulger Gene: kcna1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.434 | KCNA1 | Rebecca Foulger commented on gene: KCNA1: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Demoted KCNA1 from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.352 | KCNA1 | Rebecca Foulger Publications for gene: KCNA1 were set to 29056246; 11026449; 9581771 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.351 | KCNA1 | Rebecca Foulger edited their review of gene: KCNA1: Added comment: Added a Red review to highlight the comment from Diane Cairns (Manchester University NHS, North West GLH) that it would be acceptable to remove this gene from the Epilepsy Panel.; Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.263 | KCNA1 | Rebecca Foulger Source North West GLH was added to KCNA1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.262 | KCNA1 | Rebecca Foulger commented on gene: KCNA1: Diane Cairns (Manchester University NHS, North West GLH) comments that "I have looked into the variants that we found on our Epilepsy panel in the FLNA, SCN9A and KCNA1 genes. Using ACGS guidelines these variants are all Class 3 or below, we therefore feel that it would be acceptable to remove these genes from the Epilepsy Panel." (personal communication via email to Jane Deller, 2019-09-04) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.262 | SCN9A | Rebecca Foulger commented on gene: SCN9A: Diane Cairns (Manchester University NHS, North West GLH) comments that "I have looked into the variants that we found on our Epilepsy panel in the FLNA, SCN9A and KCNA1 genes. Using ACGS guidelines these variants are all Class 3 or below, we therefore feel that it would be acceptable to remove these genes from the Epilepsy Panel." (personal communication via email to Jane Deller, 2019-09-04) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.262 | FLNA | Rebecca Foulger commented on gene: FLNA: Diane Cairns (Manchester University NHS, North West GLH) comments that "I have looked into the variants that we found on our Epilepsy panel in the FLNA, SCN9A and KCNA1 genes. Using ACGS guidelines these variants are all Class 3 or below, we therefore feel that it would be acceptable to remove these genes from the Epilepsy Panel." (personal communication via email to Jane Deller, 2019-09-04) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.232 | KCNA1 | Rebecca Foulger Marked gene: KCNA1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.232 | KCNA1 | Rebecca Foulger Gene: kcna1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.232 | KCNA1 | Rebecca Foulger commented on gene: KCNA1: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is sufficient evidence to rate this gene Green. Kept rating as Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.191 | KCNA1 | Rebecca Foulger Source Wessex and West Midlands GLH was added to KCNA1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.190 | KCNA1 | Rebecca Foulger Source NHS GMS was added to KCNA1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.189 | KCNA1 | Rebecca Foulger reviewed gene: KCNA1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.188 | KCNA1 | Tracy Lester reviewed gene: KCNA1: Rating: AMBER; Mode of pathogenicity: ; Publications: 24578548; Phenotypes: Episodic ataxia/myokymia syndrome, 160120; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy | KCNA1 | Sarah Leigh marked gene: KCNA1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy | KCNA1 | Sarah Leigh classified KCNA1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy | KCNA1 | Sarah Leigh Added gene to panel | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||