Submissions for variant NM_006516.4(SLC2A1):c.274C>T (p.Arg92Trp)

dbSNP: rs202060209

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000426262	SCV000520909	pathogenic	not provided	2023-05-30	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26598494, 24892788, 24847886, 19630075, 26350204, 32247176, 31440721, 25564316)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000705009	SCV000833986	pathogenic	GLUT1 deficiency syndrome 1, autosomal recessive	2024-10-17	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 92 of the SLC2A1 protein (p.Arg92Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with PED and paroxysmal kinesigenic dyskinesia (PKD) and paroxysmal exercise-induced dyskinesia (PED) and GLUT1 deficiency syndrome (PMID: 19630075, 25564316, 26598494). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 16119). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic.
Raymond Lab, University of Cambridge	RCV000850197	SCV000897734	likely pathogenic	Intellectual disability	2019-02-13	criteria provided, single submitter	research
Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine	RCV001843456	SCV002102858	likely pathogenic	Developmental disorder	2021-11-19	criteria provided, single submitter	clinical testing
Laboratory of Human Genetics, Universidade de São Paulo	RCV002243647	SCV002512189	pathogenic	Encephalopathy due to GLUT1 deficiency; Childhood onset GLUT1 deficiency syndrome 2	2022-05-13	criteria provided, single submitter	research	This variant meets our criteria to be classified as pathogenic based upon segregation studies, extremely low frequency, and in-silico evaluation of pathogenicity.
Genome-Nilou Lab	RCV003445077	SCV004173571	likely pathogenic	Encephalopathy due to GLUT1 deficiency	2023-04-11	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000426262	SCV004700062	pathogenic	not provided	2024-02-01	criteria provided, single submitter	clinical testing	SLC2A1: PP1:Strong, PS2, PM2, PS4:Moderate, PP3
OMIM	RCV000017499	SCV000037771	pathogenic	Childhood onset GLUT1 deficiency syndrome 2	2009-08-15	no assertion criteria provided	literature only
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000426262	SCV001927836	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000426262	SCV001952704	pathogenic	not provided		no assertion criteria provided	clinical testing