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Genetic epilepsy syndromes

Gene: SCN8A

Green List (high evidence)

SCN8A (sodium voltage-gated channel alpha subunit 8)
EnsemblGeneIds (GRCh38): ENSG00000196876
EnsemblGeneIds (GRCh37): ENSG00000196876
OMIM: 600702, Gene2Phenotype
SCN8A is in 14 panels

9 reviews

Sarah Leigh (Genomics England Curator)

Comment on mode of pathogenicity: Based on report in PMID 31625145, reporting biallelic loss of function SCN8A variants in three cases in two families with severe developmental and epileptic encephalopathy. This differs from the previosly reported gain of function, monoallelic variants (PMID 24194747;22365152).
Created: 26 Mar 2020, 3:49 p.m. | Last Modified: 26 Mar 2020, 3:49 p.m.
Panel Version: 2.25
Comment on mode of pathogenicity: Based on report in PMID 31625145, reporting biallelic loss of function SCN8A variants in three cases in two families with severe developmental and epileptic encephalopathy.
Created: 26 Mar 2020, 3:38 p.m. | Last Modified: 26 Mar 2020, 3:38 p.m.
Panel Version: 2.24
Comment on mode of inheritance: Based on report in PMID 31625145, reporting biallelic loss of function SCN8A variants in three cases in two families with severe developmental and epileptic encephalopathy.
Created: 26 Mar 2020, 9:44 a.m. | Last Modified: 26 Mar 2020, 9:44 a.m.
Panel Version: 2.23

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Note recent publication of bi-allelic variants causing epilepsy in three individuals from two families. Mono-allelic variants are typically GoF, whereas these variants were shown to be LoF. Parents are said to have had mild learning difficulties. Consider changing mode of inheritance and pathogenicity and associated pipeline settings.
Created: 21 Jan 2020, 10:34 a.m. | Last Modified: 21 Jan 2020, 10:34 a.m.
Panel Version: 2.0

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Epileptic encephalopathy, early infantile, 13, MIM# 614558; dominant and recessive

Publications

Mode of pathogenicity
Other

Variants in this GENE are reported as part of current diagnostic practice

Rebecca Foulger (Genomics England curator)

I don't know

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.
Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

AD cognitive impairment with/without cerebellar ataxia, AD EIEE 13, AD benign familial infantile seizures. Lots of mutations reported - mostly missense on HGMD pro in assocation with an epilepsy phentoye. Several cases on OMIM with variants detected, arisen de novo. Functional studies have been undertaken for some variants: Veeramah et al, 2012 & de Kovel et al, 2014.
Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
?Cognitive impairment with or without cerebellar ataxia,614306; Epileptic encephalopathy, early infantile,614558; Seizures, benign familial infantile,617080

Publications

Amy McTague (UCL Institute of Child Health)

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Cognitive impairment with or without cerebellar ataxia; Intellectual disability; Epileptic encephalopathy, early infantile, 13

Publications

  • Trudeau et al (2004) J Med Genet 43: 527_530
  • O'Brien and Meisler (2013) Frontiers in Genet 4(213): 1-9
  • Veeramah et al (2012) Am J Hum Genet 90: 502_510

Variants in this GENE are reported as part of current diagnostic practice

Natalie Trump (NHS - Great Ormond Street Hospital)

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Cognitive impairment with or without cerebellar ataxia; Intellectual disability; Epileptic encephalopathy, early infantile, 13

Publications

  • Trudeau et al (2004) J Med Genet 43: 527_530
  • O'Brien and Meisler (2013) Frontiers in Genet 4(213): 1-9
  • Veeramah et al (2012) Am J Hum Genet 90: 502_510

Variants in this GENE are reported as part of current diagnostic practice

Manju Kurian (UCL-Institute of Child Health)

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Cognitive impairment with or without cerebellar ataxia; Intellectual disability; Epileptic encephalopathy, early infantile, 13

Publications

  • Trudeau et al (2004) J Med Genet 43: 527_530
  • O'Brien and Meisler (2013) Frontiers in Genet 4(213): 1-9
  • Veeramah et al (2012) Am J Hum Genet 90: 502_510

Variants in this GENE are reported as part of current diagnostic practice

Richard Scott (North Thames GMC/UCL)

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cognitive impairment with or without cerebellar ataxia; Intellectual disability; Epileptic encephalopathy, early infantile, 13

Publications

  • Trudeau et al (2004) J Med Genet 43: 527 530
  • O'Brien and Meisler (2013) Frontiers in Genet 4(213): 1-9
  • Veeramah et al (2012) Am J Hum Genet 90: 502 510

Mode of pathogenicity
loss-of-function (truncating variants and curated list of variants)

Variants in this GENE are reported as part of current diagnostic practice

Ellen McDonagh (Genomics England Curator)

Comment when marking as ready: Confirmed DD gene and all 4 reviewers agree this should be green. Mode of inheritance confirmed. Mutation consequence summary from G2P is dominant negative.
Created: 21 Jan 2016, 12:53 p.m.
Comment on mode of inheritance: Confirmed and not on imprinted gene list.
Created: 21 Jan 2016, 11:57 a.m.

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • NIHRBR-RD Consortium SPEED_v3.0_20170404
  • Victorian Clinical Genetics Services
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Expert Review Green
Phenotypes
  • ?Cognitive impairment with or without cerebellar ataxia,614306
  • Epileptic encephalopathy, early infantile,614558
  • Seizures, benign familial infantile,617080
OMIM
600702
Clinvar variants
Variants in SCN8A
Penetrance
None
Publications
Mode of Pathogenicity
Other
Panels with this gene

History Filter Activity

26 Mar 2020, Gel status: 3

Set mode of pathogenicity

Sarah Leigh (Genomics England Curator)

Mode of pathogenicity for gene: SCN8A was changed from Other to Other

26 Mar 2020, Gel status: 3

Set mode of pathogenicity

Sarah Leigh (Genomics England Curator)

Mode of pathogenicity for gene: SCN8A was changed from None to Other

26 Mar 2020, Gel status: 3

Set mode of inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for gene: SCN8A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

26 Mar 2020, Gel status: 3

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: SCN8A were changed from Cognitive impairment with or without cerebellar ataxia; Intellectual disability; Epileptic encephalopathy, early infantile, 13 to ?Cognitive impairment with or without cerebellar ataxia,614306; Epileptic encephalopathy, early infantile,614558; Seizures, benign familial infantile,617080

26 Mar 2020, Gel status: 3

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: SCN8A were set to Trudeau et al (2004) J Med Genet 43: 527_530; O'Brien and Meisler (2013) Frontiers in Genet 4(213): 1-9; Veeramah et al (2012) Am J Hum Genet 90: 502_510

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to SCN8A.

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to SCN8A.

11 Dec 2018, Gel status: 4

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Ellen McDonagh: Comment on mode of inheritance

26 Jun 2018, Gel status: 4

Added New Source

Sarah Leigh (Genomics England Curator)

NIHRBR-RD Consortium SPEED_v3.0_20170404 was added to SCN8A. Panel: Genetic Epilepsy Syndromes

25 Jun 2018, Gel status: 4

Added New Source

Sarah Leigh (Genomics England Curator)

Victorian Clinical Genetics Services was added to SCN8A. Panel: Genetic Epilepsy Syndromes

4 Apr 2018, Gel status: 4

Added New Source

Sarah Leigh (Genomics England Curator)

SCN8A was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review Green,UKGTN,Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services

4 Apr 2018, Gel status: 4

Created

Sarah Leigh (Genomics England Curator)

SCN8A was created by Sarah Leigh