Submissions for variant NM_006516.4(SLC2A1):c.940G>A (p.Gly314Ser)

dbSNP: rs121909739

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000153967	SCV000232239	pathogenic	not provided	2014-01-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000153967	SCV000329809	pathogenic	not provided	2022-02-28	criteria provided, single submitter	clinical testing	Published functional studies demonstrate reduced glucose uptake (Weber et al., 2008); Not observed in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 20574033, 27781031, 26615598, 18451999, 26986070, 21791420, 20507906, 25022942, 27351150, 26536893, 27128978, 26821218, 24847886, 11076005, 30895386, 31302675, 33584489)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000473987	SCV000545828	pathogenic	GLUT1 deficiency syndrome 1, autosomal recessive	2024-03-28	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 314 of the SLC2A1 protein (p.Gly314Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with epilepsy, mild mental retardation, and impulsivity and/or paroxysmal exertion-induced dyskinesias (PMID: 11076005, 18451999, 26615598, 27351150). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 16113). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SLC2A1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects SLC2A1 function (PMID: 18451999). For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center	RCV001253635	SCV001429464	pathogenic	Encephalopathy due to GLUT1 deficiency	2018-06-13	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000153967	SCV001446492	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000153967	SCV002496865	pathogenic	not provided	2023-05-01	criteria provided, single submitter	clinical testing	SLC2A1: PM2, PM5, PS2:Moderate, PS4:Moderate, PP2, PS3:Supporting
MGZ Medical Genetics Center	RCV002288509	SCV002581027	pathogenic	Dystonia 9	2022-07-19	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001253635	SCV004172865	pathogenic	Encephalopathy due to GLUT1 deficiency	2023-04-11	criteria provided, single submitter	clinical testing
OMIM	RCV000017493	SCV000037765	pathogenic	Childhood onset GLUT1 deficiency syndrome 2	2008-06-01	no assertion criteria provided	literature only
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000153967	SCV001809509	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000153967	SCV001955691	pathogenic	not provided		no assertion criteria provided	clinical testing