ClinVar Miner

Submissions for variant NM_001365088.1(SLC12A6):c.3400C>T (p.Arg1134Ter)

gnomAD frequency: 0.00003  dbSNP: rs606231229
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000023393 SCV000791898 likely pathogenic Agenesis of the corpus callosum with peripheral neuropathy 2017-05-31 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000023393 SCV002572422 pathogenic Agenesis of the corpus callosum with peripheral neuropathy 2022-08-29 criteria provided, single submitter clinical testing Variant summary: SLC12A6 c.3400C>T (p.Arg1134X), located in the last exon (exon 25) results in a premature termination codon predicted to cause a truncation of the last 17 amino acid residues at the C-terminal end of the encoded protein. The variant allele was found at a frequency of 8e-06 in 250814 control chromosomes. c.3400C>T has been reported in the literature as a homozygous genotype in two individuals from one family affected with features of Hereditary motor and sensory neuropathy with agenesis of the corpus callosum (Andermann Syndrome) (example, Salin-Cantegrel_2011). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function demonstrating a loss of interaction with CK-B, the braintype creatine kinase (CK-B), which is an ATP-generating protein and a potent activator of SLC12A6 (KCC3) via a direct interaction with the carboxyl-terminal domain of the co-transporter (Salin-Cantegrel_2011). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics RCV000023393 SCV004201193 pathogenic Agenesis of the corpus callosum with peripheral neuropathy 2022-07-22 criteria provided, single submitter clinical testing
OMIM RCV000023393 SCV000044684 pathogenic Agenesis of the corpus callosum with peripheral neuropathy 2011-08-12 no assertion criteria provided literature only
Inherited Neuropathy Consortium RCV000790222 SCV000929614 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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