Submissions for variant NM_006516.4(SLC2A1):c.695G>A (p.Arg232His)

gnomAD frequency: 0.00001  dbSNP: rs139412383

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000761654	SCV000891825	likely pathogenic	not provided	2018-09-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000761654	SCV001988948	uncertain significance	not provided	2023-09-20	criteria provided, single submitter	clinical testing	Identified in a patient with early onset absence epilepsy, but it is unknown whether this individual was screened for variants in other genes associated with epilepsy (PMID: 26537434); 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: 26537434)
Institute of Human Genetics, University of Leipzig Medical Center	RCV001823005	SCV002072542	likely pathogenic	Epilepsy, idiopathic generalized, susceptibility to, 12	2022-01-04	criteria provided, single submitter	clinical testing	_x000D_ Criteria applied: PS4_MOD, PM5, PM2_SUP, PP3
Labcorp Genetics (formerly Invitae), Labcorp	RCV001855704	SCV002315993	likely pathogenic	GLUT1 deficiency syndrome 1, autosomal recessive	2021-03-10	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with histidine at codon 232 of the SLC2A1 protein (p.Arg232His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Arg232 amino acid residue in SLC2A1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22282645, Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. This variant has been observed in individual(s) with absence seizures with or without intellectual disability (PMID: 26537434). ClinVar contains an entry for this variant (Variation ID: 623683). This variant is present in population databases (rs139412383, ExAC 0.01%).