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Arthrogryposis

Gene: SCN1A

Amber List (moderate evidence)

SCN1A (sodium voltage-gated channel alpha subunit 1)
EnsemblGeneIds (GRCh38): ENSG00000144285
EnsemblGeneIds (GRCh37): ENSG00000144285
OMIM: 182389, Gene2Phenotype
SCN1A is in 15 panels

2 reviews

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Note we have reported this association previously in PMID 29543227 (Supplementary info) in an infant presenting with AMC and severe EE, and de novo p.(Ile1347Asn) variant which at the time was thought to only partially explain the phenotype, but in light of this new report, likely fully explains the phenotype. Given the presence of severe seizure disorder in the two infants who were phenotyped in the newborn period, this likely represents the severe end of the spectrum of SCN1A-related disorders rather than a distinct association.
Created: 2 Oct 2020, 10:17 p.m. | Last Modified: 2 Oct 2020, 10:17 p.m.
Panel Version: 3.13

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Arthrogryposis multiplex congenita; Dravet syndrome, MIM# 607208

Publications

Arina Puzriakova (Genomics England Curator)

I don't know

Comment on list classification: There are sufficient unrelated cases (4) reported in 2 papers (PMIDs: 32928894 and 29543227) with ACM and variants in this gene.

It is anticipated that early-onset seizures likely represent the predominant feature of the disease presentation (already Green on the Genetic epilepsy syndromes panel), however this gene will be flagged for review to assess whether inclusion on this panel is likely to be of clinical benefit.
Created: 2 Dec 2020, 2:44 p.m. | Last Modified: 2 Dec 2020, 2:44 p.m.
Panel Version: 3.18
Note SCN1A is a well-established cause of Dravet syndrome, MIM# 607208
Created: 2 Oct 2020, 4:09 p.m. | Last Modified: 2 Oct 2020, 4:09 p.m.
Panel Version: 3.13
Comment on list classification: Association with this phenotype currently based on a single publication, although reporting 3 unrelated cases.

Rating Amber, awaiting further publications/clinical evidence to validate this gene-disease relationship.
Created: 2 Oct 2020, 4:05 p.m. | Last Modified: 2 Oct 2020, 4:05 p.m.
Panel Version: 3.13
PMID: 32928894 (2020) - De novo missense variants in SCN1A (p.Leu893Phe, p.Ala989Thr, p.Ile236Thr) were identified in three unrelated patients with AMC which was diagnosed from the second trimester of pregnancy. One patient developed intractable epilepsy from birth and died at 21 days, while the other two pregnancies were terminated. No functional studies of the variants or patient cells were performed.
Sources: Literature
Created: 2 Oct 2020, 4 p.m.

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

Phenotypes
Arthrogryposis multiplex congenita

Publications

History Filter Activity

2 Dec 2020, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: scn1a has been classified as Amber List (Moderate Evidence).

2 Dec 2020, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: SCN1A were changed from Arthrogryposis multiplex congenita to Arthrogryposis multiplex congenita; Dravet syndrome, OMIM:607208

2 Dec 2020, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: SCN1A were set to 32928894

2 Dec 2020, Gel status: 2

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag for-review tag was added to gene: SCN1A.

2 Oct 2020, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: scn1a has been classified as Amber List (Moderate Evidence).

2 Oct 2020, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Arina Puzriakova (Genomics England Curator)

gene: SCN1A was added gene: SCN1A was added to Arthrogryposis. Sources: Literature Mode of inheritance for gene: SCN1A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SCN1A were set to 32928894 Phenotypes for gene: SCN1A were set to Arthrogryposis multiplex congenita Review for gene: SCN1A was set to AMBER