Submissions for variant NM_001365088.1(SLC12A6):c.2023C>T (p.Arg675Ter)

dbSNP: rs121908428

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000005653	SCV000699838	pathogenic	Agenesis of the corpus callosum with peripheral neuropathy	2017-08-22	criteria provided, single submitter	clinical testing	Variant summary: The SLC12A6 c.2023C>T (p.Arg675X) variant results in a premature termination codon, predicted to cause a truncated or absent SLC12A6 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This variant is absent in 121074 control chromosomes. A publication cites the variant in two homozygous siblings affected witn Andermann Syndrome. In addition, multiple reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae	RCV001045904	SCV001209779	pathogenic	not provided	2022-11-13	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 5327). This premature translational stop signal has been observed in individual(s) with agenesis of the corpus callosum with peripheral neuropathy (PMID: 12368912). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg675*) in the SLC12A6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC12A6 are known to be pathogenic (PMID: 12368912, 16606917).
Genome-Nilou Lab	RCV000005653	SCV002055414	pathogenic	Agenesis of the corpus callosum with peripheral neuropathy	2021-07-15	criteria provided, single submitter	clinical testing
OMIM	RCV000005653	SCV000025835	pathogenic	Agenesis of the corpus callosum with peripheral neuropathy	2002-11-01	no assertion criteria provided	literature only
GeneReviews	RCV000005653	SCV000166718	not provided	Agenesis of the corpus callosum with peripheral neuropathy		no assertion provided	literature only
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000005653	SCV000733433	likely pathogenic	Agenesis of the corpus callosum with peripheral neuropathy		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001045904	SCV001923690	pathogenic	not provided		no assertion criteria provided	clinical testing