Skeletal muscle channelopathy

Gene: SLC1A3

Green List (high evidence)

SLC1A3 (solute carrier family 1 member 3)
EnsemblGeneIds (GRCh38): ENSG00000079215
EnsemblGeneIds (GRCh37): ENSG00000079215
OMIM: 600111, Gene2Phenotype
SLC1A3 is in 14 panels

3 reviews

Eleanor Williams (Genomics England Curator)

Red List (low evidence)

Comment on list classification: Leaving rating as Green but with a recommendation for review by the GMS test evaluation group as to suitability for this panel. Variants seem to result in a brain channelopathy rather than a skeletal muscle one.
Created: 9 Jun 2021, 2:54 p.m. | Last Modified: 20 Jul 2021, 2:06 p.m.
Panel Version: 1.31
3 reports in the literature of variants in this gene associated with Episodic ataxia, type 6. These reports suggest a brain channelopathy rather than a skeletal muscle channelopathy.

PMID: 16116111 - Jen et al 2005 - report a 10 yo patient with episodic ataxia, seizures, migraine, and alternating hemiplegia who was found to have a heterozygous mutation in SLC1A3 through screening of this gene. Functional studies in mammalian cell lines showed decreased glutamate uptake, which can contribute to neuronal hyperexcitability.

PMID: 19139306 - de Vries et al 2009 - following analysis of SLC1A3 they report a 35 year old, who has had episodes of ataxia since early childhood, with a heterozygous c.556 T>A (C186S) variant. Nausea, vomiting, photophobia, phonophobia, vertigo, diplopia, slurred speech, and blurred vision often also occur with attacks. His carrier mother and sister were also affected, but a carrier cousin is unaffected cousin. Functional studies using COS7 cells (fibroblast like) show that the variant reduces glutamate uptake compared to wild type protein.

PMID: 25497598 - Pyle et al 2015 - report a 30 yo male who presented with speech disturbance, dexterity problems and a deteriorating gait. His mother and cousin are also affected. The two cousins were found to have a heterozygous variant in SLC1A3 c.1361G>A:p.Arg454Gln. The disorder was not described as episodic.
Created: 9 Jun 2021, 2:51 p.m. | Last Modified: 9 Jun 2021, 2:51 p.m.
Panel Version: 1.26

Phenotypes
Episodic ataxia, type 6, OMIM:612656; episodic ataxia type 6, MONDO:0012982

Publications

Zornitza Stark (Australian Genomics)

Red List (low evidence)

This is a brain channelopathy.
Created: 20 Aug 2020, 8:53 a.m. | Last Modified: 20 Aug 2020, 8:53 a.m.
Panel Version: 1.4

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Episodic ataxia, type 6, MIM# 612656

James Polke (Neurogenetics Laboratory, Institute of Neurology, London)

Green List (high evidence)

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

Phenotypes
Episodic ataxia, type 6, 612656

Publications

  • de Vries et al 2009 Arch Neurol 66. 97-101 PMID: 19139306

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

History Filter Activity

20 Jul 2021, Gel status: 3

Removed Tag

Eleanor Williams (Genomics England Curator)

Tag Q2_21_rating was removed from gene: SLC1A3.

9 Jun 2021, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: slc1a3 has been classified as Green List (High Evidence).

9 Jun 2021, Gel status: 3

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: SLC1A3 were changed from Episodic ataxia, type 6, 612656 to Episodic ataxia, type 6, OMIM:612656; episodic ataxia type 6, MONDO:0012982

9 Jun 2021, Gel status: 3

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: SLC1A3 were set to 19139306

9 Jun 2021, Gel status: 3

Added Tag

Eleanor Williams (Genomics England Curator)

Tag Q2_21_phenotype tag was added to gene: SLC1A3.

9 Jun 2021, Gel status: 3

Added Tag

Eleanor Williams (Genomics England Curator)

Tag Q2_21_rating tag was added to gene: SLC1A3.

25 Oct 2019, Gel status: 3

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene SLC1A3 were changed from to 19139306

25 Oct 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to SLC1A3.

25 Oct 2019, Gel status: 3

Set mode of inheritance, Set Phenotypes

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene SLC1A3 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Added phenotypes Episodic ataxia, type 6, 612656 for gene: SLC1A3

25 Oct 2019, Gel status: 3

Added New Source, Status Update

Louise Daugherty (Genomics England Curator)

Source Expert Review Green was added to SLC1A3. Rating Changed from Red List (low evidence) to Green List (high evidence)

25 Oct 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Louise Daugherty (Genomics England Curator)

gene: SLC1A3 was added gene: SLC1A3 was added to Myotonia congenita. Sources: London North GLH Mode of inheritance for gene: SLC1A3 was set to