ClinVar Miner

Submissions for variant NM_006516.3(SLC2A1):c.1372C>T (p.Arg458Trp) (rs13306758)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000762930 SCV000893352 likely pathogenic Stomatin-deficient cryohydrocytosis with neurologic defects; Dystonia 9; GLUT1 deficiency syndrome 1; GLUT1 deficiency syndrome 2; Epilepsy, idiopathic generalized, susceptibility to, 12 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000423069 SCV000515871 likely pathogenic not provided 2017-01-23 criteria provided, single submitter clinical testing A variant that is likely pathogenic has been identified in the SLC2A1 gene. The R458Q variant as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. However a different amino acid substitution at the same position (R458W) has been previously reported in association with idiopathic generalized epilepsy is two other families and functional studies showed the R458W variant caused a decrease in glucose transport in Xenopus oocytes. (Arsov et al., 2012; Tzadok et al., 2014). R458Q was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In silico analysis predicts this variant is probably damaging to the protein structure/function. The R458Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Additionally, this variant was identified as a de novo change in an individual tested at GeneDx. This substitution occurs at a position where amino acids with similar properties to Arginine are tolerated across species, and Glutamine is observed at this position in another mammal species.Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Invitae RCV000701550 SCV000830354 pathogenic GLUT1 deficiency syndrome 1, autosomal recessive 2018-11-09 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 458 of the SLC2A1 protein (p.Arg458Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with seizures in families (PMID: 25564316, Invitae). This variant has been reported in individuals affected with generalized epilepsy as well as an unaffected relative (PMID: 23280796, 23340081, 28116237). ClinVar contains an entry for this variant (Variation ID: 96708). Experimental studies have shown that this missense change in Xenopus resulted in reduced glucose transport activity (PMID: 23280796). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000082868 SCV000114919 risk factor Epilepsy, idiopathic generalized, susceptibility to, 12 2012-11-01 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.