Submissions for variant NM_006516.4(SLC2A1):c.1408G>T (p.Gly470Trp)

dbSNP: rs572648977

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000189383	SCV000243021	uncertain significance	not provided	2015-06-16	criteria provided, single submitter	clinical testing	p.Gly470Trp (G470W) GGG>TGG: c.1408 G>T in exon 10 of the SLC2A1 gene (NM_006516.2) The G470W variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It 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. The G470W variant is a semi-D2 conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across mammals but is not conserved in more distantly related species in evolution. A missense mutation in a nearby residue (R468W) has been reported in association with Glut1-DS. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, the possibility that it is a disease-associated mutation cannot be excluded since some individuals with SLC2A1 mutations have been reported to be mildly affected or unaffected due to variability in phenotypic expression and/or reduced penetrance (Mullen et al., 2010; Weber et al., 2008; Suls et al., 2008). The variant is found in EPILEPSY panel(s).
CeGaT Center for Human Genetics Tuebingen	RCV000189383	SCV001147234	uncertain significance	not provided	2016-06-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001054891	SCV001219249	uncertain significance	GLUT1 deficiency syndrome 1, autosomal recessive	2022-10-03	criteria provided, single submitter	clinical testing	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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SLC2A1 protein function. ClinVar contains an entry for this variant (Variation ID: 207217). This variant has not been reported in the literature in individuals affected with SLC2A1-related conditions. This variant is present in population databases (rs572648977, gnomAD 0.02%). This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 470 of the SLC2A1 protein (p.Gly470Trp).
Genome-Nilou Lab	RCV003445676	SCV004172253	uncertain significance	Epilepsy, idiopathic generalized, susceptibility to, 12	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003445675	SCV004172254	uncertain significance	Dystonia 9	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003445673	SCV004172255	uncertain significance	Encephalopathy due to GLUT1 deficiency	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003445674	SCV004172256	uncertain significance	Childhood onset GLUT1 deficiency syndrome 2	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003445677	SCV004172257	uncertain significance	Hereditary cryohydrocytosis with reduced stomatin	2023-04-11	criteria provided, single submitter	clinical testing