Submissions for variant NM_006516.4(SLC2A1):c.601T>G (p.Cys201Gly)

gnomAD frequency: 0.00001  dbSNP: rs1050933017

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology	RCV001028107	SCV001190893	uncertain significance	Childhood onset GLUT1 deficiency syndrome 2	2019-10-31	criteria provided, single submitter	research
Labcorp Genetics (formerly Invitae), Labcorp	RCV001321659	SCV001512498	uncertain significance	GLUT1 deficiency syndrome 1, autosomal recessive	2023-12-06	criteria provided, single submitter	clinical testing	This sequence change replaces cysteine, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 201 of the SLC2A1 protein (p.Cys201Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SLC2A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 828198). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is not expected to disrupt SLC2A1 function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
CeGaT Center for Human Genetics Tuebingen	RCV001532532	SCV001748137	uncertain significance	not provided	2021-03-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001532532	SCV001992720	uncertain significance	not provided	2021-07-22	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
PreventionGenetics, part of Exact Sciences	RCV004553563	SCV004116546	uncertain significance	SLC2A1-related disorder	2022-11-29	criteria provided, single submitter	clinical testing	The SLC2A1 c.601T>G variant is predicted to result in the amino acid substitution p.Cys201Gly. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-43395622-A-C). An alternate missense change at the same amino acid position has been reported in individuals affected with SLC2A1 related disorders (Gardiner et al. 2015. PubMed ID: 26598494; Magrinelli et al. 2020. PubMed ID: 32753446). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Genome-Nilou Lab	RCV003446591	SCV004173385	uncertain significance	Epilepsy, idiopathic generalized, susceptibility to, 12	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003446590	SCV004173386	uncertain significance	Dystonia 9	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003446589	SCV004173387	uncertain significance	Encephalopathy due to GLUT1 deficiency	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001028107	SCV004173388	uncertain significance	Childhood onset GLUT1 deficiency syndrome 2	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003446592	SCV004173390	uncertain significance	Hereditary cryohydrocytosis with reduced stomatin	2023-04-11	criteria provided, single submitter	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001532532	SCV001800566	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001532532	SCV001971583	uncertain significance	not provided		no assertion criteria provided	clinical testing