Submissions for variant NM_006516.4(SLC2A1):c.1402C>T (p.Arg468Trp)

dbSNP: rs267607059

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000017500	SCV000831425	pathogenic	GLUT1 deficiency syndrome 1, autosomal recessive	2022-08-16	criteria provided, single submitter	clinical testing	This missense change has been observed in individual(s) with SLC2A1-related conditions (PMID: 20221955, 20687207; Invitae). It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 16120). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 468 of the SLC2A1 protein (p.Arg468Trp).
GeneDx	RCV001548577	SCV001768511	uncertain significance	not provided	2021-03-02	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); 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: 20687207, 20221955, 29303961, 24847886)
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001548577	SCV001905594	likely pathogenic	not provided	2021-09-15	criteria provided, single submitter	clinical testing
OMIM	RCV000017500	SCV000037772	pathogenic	GLUT1 deficiency syndrome 1, autosomal recessive	2009-10-01	no assertion criteria provided	literature only
GeneReviews	RCV002271988	SCV002556357	not provided	Encephalopathy due to GLUT1 deficiency		no assertion provided	literature only
PreventionGenetics, part of Exact Sciences	RCV004737155	SCV005356401	likely pathogenic	SLC2A1-related disorder	2024-06-21	no assertion criteria provided	clinical testing	The SLC2A1 c.1402C>T variant is predicted to result in the amino acid substitution p.Arg468Trp. This variant has been reported in the homozygous state in individuals with glucose transporter type 1 deficiency syndrome (Klepper et al. 2009. PubMed ID: 20221955; Rotstein et al. 2010. PubMed ID: 20687207). This variant has not been reported in a large population database, indicating this variant is rare. This variant is interpreted as likely pathogenic.