Submissions for variant NM_006516.4(SLC2A1):c.1297G>A (p.Val433Ile)

gnomAD frequency: 0.00001  dbSNP: rs200819771

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001569790	SCV001793940	likely benign	not provided	2020-08-26	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003298932	SCV003992356	likely benign	Inborn genetic diseases	2023-06-05	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Genome-Nilou Lab	RCV003446835	SCV004172299	likely benign	Epilepsy, idiopathic generalized, susceptibility to, 12	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003446834	SCV004172300	likely benign	Dystonia 9	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003446832	SCV004172301	likely benign	Encephalopathy due to GLUT1 deficiency	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003446833	SCV004172302	likely benign	Childhood onset GLUT1 deficiency syndrome 2	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003446836	SCV004172303	likely benign	Hereditary cryohydrocytosis with reduced stomatin	2023-04-11	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV003771735	SCV004621803	uncertain significance	GLUT1 deficiency syndrome 1, autosomal recessive	2024-09-15	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 433 of the SLC2A1 protein (p.Val433Ile). This variant is present in population databases (rs200819771, gnomAD 0.004%). 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: 1203673). Invitae Evidence 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 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. 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.