Intellectual disability - microarray and sequencing
Gene: SCN8AComment on mode of inheritance: MOI was changed back from "Both monoallelic and biallelic" to "Monoallelic", which reflects the original MOI of the signed off panel (version 3.2). The MOI will be changed back to "Both monoallelic and biallelic" after the panel has been reviewed.Created: 14 Jan 2021, 1:26 p.m. | Last Modified: 14 Jan 2021, 1:26 p.m.
Panel Version: 3.704
Added 'for-review' tag as the MOI has changed since previous sign-off of this panel (version 3.2) and requires review by the Specialist Test Group.Created: 21 Oct 2020, 4:44 p.m. | Last Modified: 21 Oct 2020, 4:44 p.m.
Panel Version: 3.483
Just 2 families reported with possible AR inheritance: v rare - all het parents seem to have features so prob ok to keep as monoallelic only (source NHS Genomic Medicine Service).Created: 9 Mar 2022, 3:40 p.m. | Last Modified: 9 Mar 2022, 3:40 p.m.
Panel Version: 3.1510
After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changedCreated: 9 Mar 2022, 3:40 p.m. | Last Modified: 9 Mar 2022, 3:40 p.m.
Panel Version: 3.1510
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: 3.23
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, 9:43 a.m. | Last Modified: 26 Mar 2020, 9:43 a.m.
Panel Version: 3.22
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
COGNITIVE IMPAIRMENT WITH OR WITHOUT CEREBELLAR ATAXIA
Publications
This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf;in_gilissen_2014_known;in_omim_20150205_epilepsies;in_omim_20150205_movement . Main mutation mechanism : Dominant negative; Loss of functionCreated: 27 Jul 2017, 8:20 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; find_uk10k; gilissen_2014_known; omim_20150205_epilepsies; omim_20150205_movement; sfari_20150206; Nijmegen_ID_diagnostic; Nijmegen_ID_candidates; GEL_ID_green_20160217; neuro_20160418_strict; Dominant negative; Loss of function. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation TrustCreated: 19 Jul 2017, 1:19 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications
Mode of pathogenicity
Tag for-review was removed from gene: SCN8A.
Phenotypes for gene: SCN8A were changed from ?Cognitive impairment with or without cerebellar ataxia,614306; Epileptic encephalopathy, early infantile,614558; Seizures, benign familial infantile,617080 to Cognitive impairment with or without cerebellar ataxia, OMIM:614306; Developmental and epileptic encephalopathy 13, OMIM:614558
Mode of inheritance for gene: SCN8A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Tag for-review tag was added to gene: SCN8A.
Mode of pathogenicity for gene: SCN8A was changed from to Other
Mode of inheritance for gene: SCN8A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: SCN8A were changed from Cognitive impairment with or without cerebellar ataxia, 614306Epileptic encephalopathy, early infantile, 13, 614558; COGNITIVE IMPAIRMENT WITH OR WITHOUT CEREBELLAR ATAXIA to ?Cognitive impairment with or without cerebellar ataxia,614306; Epileptic encephalopathy, early infantile,614558; Seizures, benign familial infantile,617080
Publications for gene: SCN8A were set to
Source Victorian Clinical Genetics Services was added to SCN8A.
12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.
The Gel status was updated for this whole panel
The Gel status was updated for this whole panel
SCN8A was added to Intellectual disabilitypanel. Source: Expert Review Green Model of inheritance for gene SCN8A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
SCN8A was added to Intellectual disabilitypanel. Sources: Radboud University Medical Center, Nijmegen