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Hereditary neuropathy NOT PMP22 copy number

Gene: SLC12A6

Amber List (moderate evidence)

SLC12A6 (solute carrier family 12 member 6)
EnsemblGeneIds (GRCh38): ENSG00000140199
EnsemblGeneIds (GRCh37): ENSG00000140199
OMIM: 604878, Gene2Phenotype
SLC12A6 is in 7 panels

8 reviews

Sarah Leigh (Genomics England Curator)

For-review tag has been added as it maybe appropriate to change the MOI to BOTH monoallelic and biallelic, autosomal or pseudoautosomal at the next major review, to ensure that de novo heterozgous variants are identified.
Created: 13 Jul 2020, 3:33 p.m. | Last Modified: 13 Jul 2020, 3:33 p.m.
Panel Version: 1.6
Associated with Agenesis of the corpus callosum with peripheral neuropathy 218000 in OMIM and as confirmed Gen2Phen gene. At least 10 biallelic variants were reported in at least 10 unrelated cases. 9/10 of these variants was terminating (PMID 12368912, 16606917, 17893295). Three de novo heterozygous missense variants have been identified in four unrelated cases with a milder phenotype of early- onset progressive Charcot- Marie-tooth disease (CMT) with or without spasticity (intermediate CMT)(PMID 31439721, 27485015). The authors of PMID 31439721 suggest that "autosomal- dominant inheritance of SLC12A6 variants also needs to be considered in patients with early- onset neuropathies". Furthermore, it will be important to understand the functional differences between the variants, as PMID 27485015 reported variant - p.Thr991Ala, resulted in increased potassium influx in Xenopus oocytes (gain-of-function), while the other missense variants identified so far had a loss-of-function effect in varying degrees (PMID 31439721).
Created: 13 Jul 2020, 3:33 p.m. | Last Modified: 13 Jul 2020, 3:33 p.m.
Panel Version: 1.6

Natalie Forrester (SWGLH - Bristol Genetics)

Green List (high evidence)

2 unrelated patients with reported variants in Bristol. In one family two affected sibs were both found to be compound heterozygous. PMID: 12368912 - reported mice with a targeted deletion of the Slc12a6 gene had a locomotor deficit, peripheral neuropathy, and a sensorimotor gating deficit, similar to the human disease
Created: 29 Apr 2019, 12:30 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum

Publications

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

Louise Daugherty (Genomics England Curator)

I don't know

Comment on list classification: Gene included in a list of complex neuropathy syndrome genes recommended to be downgraded for R78 panel (list submitted by Alex Rossor 15th July 2019)
Created: 6 Dec 2019, 8:28 p.m. | Last Modified: 6 Dec 2019, 8:28 p.m.
Panel Version: 0.66
This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Created: 6 Dec 2019, 8:27 p.m. | Last Modified: 6 Dec 2019, 8:27 p.m.
Panel Version: 0.65
Rating and review submitted on behalf of James Polke (Neurogenetics Laboratory,Institute of Neurology, London), on behalf of London North GLH for GMS Neurology specialist test group.
Created: 9 May 2019, 5 p.m.
Review and rating submitted by Natalie Forrester (SWGLH - Bristol Genetics) on behalf of South West GLH for GMS Neurology specialist test group.
Created: 29 Apr 2019, 12:53 p.m.

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

Green List (high evidence)

Rita Horvath (Institute of Genetic Medicine, Newcastle University)

Green List (high evidence)

Thalia Antoniadi (West Midlands Regional Genetics Laboratory)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Alexander Rossor (UCL Institute of Neurology)

Green List (high evidence)

Complex phenotype, notpure CMT
Created: 9 Dec 2015, 8:49 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Mary Reilly (Institute of Neurology)

Green List (high evidence)

Complex phenotype, notpure CMT
Created: 8 Dec 2015, 3:05 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • South West GLH
  • UKGTN
  • Emory Genetics Laboratory
  • Expert list
  • London North GLH
  • Illumina TruGenome Clinical Sequencing Services
  • NHS GMS
  • South West GLH
  • NHS GMS
  • London North GLH
Phenotypes
  • Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum
Tags
for-review
OMIM
604878
Clinvar variants
Variants in SLC12A6
Penetrance
None
Publications
Panels with this gene

History Filter Activity

13 Jul 2020, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: SLC12A6 were set to 12368912

13 Jul 2020, Gel status: 2

Added Tag

Sarah Leigh (Genomics England Curator)

Tag for-review tag was added to gene: SLC12A6.

6 Dec 2019, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: slc12a6 has been classified as Amber List (Moderate Evidence).

5 Dec 2019, Gel status: 3

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

Ellen McDonagh (Genomics England Curator)

gene: SLC12A6 was added gene: SLC12A6 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,Illumina TruGenome Clinical Sequencing Services,London North GLH,Expert list,Emory Genetics Laboratory,UKGTN,Expert Review Green,South West GLH Mode of inheritance for gene: SLC12A6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC12A6 were set to 12368912 Phenotypes for gene: SLC12A6 were set to Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum