Submissions for variant NM_006516.4(SLC2A1):c.1001G>A (p.Arg334Gln)

gnomAD frequency: 0.00002  dbSNP: rs892715050

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000624225	SCV000741090	uncertain significance	Inborn genetic diseases	2024-10-25	criteria provided, single submitter	clinical testing	The alteration results in an amino acid change: The c.1001G>A (p.R334Q) alteration is located in exon 8 (coding exon 8) of the SLC2A1 gene. This alteration results from a G to A substitution at nucleotide position 1001, causing the arginine (R) at amino acid position 334 to be replaced by a glutamine (Q). The alteration is not observed in population databases: Based on data from the Genome Aggregation Database (gnomAD), the SLC2A1 c.1001G>A alteration was not observed, with coverage at this position. A nearby alteration has been observed in affected individuals: Alaterations in an adjacent amino acid (p.R333), have been described in multiple patients with various phenotypes caused by GLUT1 deficiency. Mullen et al. (2011) reported two patients heterozygous for c.997C>T (p.R333W) myoclonic astatic epilepsy, paroxysmal exercise induced dyskinesia, dysarthric speech, intellectual disability, and low CSF glucose.This alteration was reported in two Japanese individuals; a 6 year old female with mild developmental delay, ataxic gait, myocloni seizures, and mild hypotonia (Takahasi, 2008) and a 2 year old boy with tonic seizures, developmental delay, cerebral atrophy, ataxic gait, and low CSF glucose (Fujii, 2007); both demonstrated dramatic improvement on a ketogenic diet (Fujii, 2007; Takahasi, 2008). Schneider et al. (2009) reported a 43 year old man with paroxysmal exercise induced dyskinesia who was heterozygous for the c.998G>A (p.R333Q) alteration; he had a history of jerky leg spasms at 4 years old following physical exercise, exercise-induced writer's cramp after prolonged writing, and myoclonic epilepsy in childhood. The altered amino acid is conserved throughout evolution: The p.R334 amino acid is conserved in available vertebrate species. The alteration is predicted inconclusive by in silico modeling: The in silico prediction for the p.R334Q alteration is inconclusive. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000802557	SCV000942394	uncertain significance	GLUT1 deficiency syndrome 1, autosomal recessive	2024-11-15	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 334 of the SLC2A1 protein (p.Arg334Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of SLC2A1-related conditions (internal data). ClinVar contains an entry for this variant (Variation ID: 520805). Invitae Evidence Modeling incorporating data from in vitro experimental studies (internal data) indicates that this missense variant is not expected to disrupt SLC2A1 function with a negative predictive value of 95%. 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.
Mayo Clinic Laboratories, Mayo Clinic	RCV001507437	SCV001712989	uncertain significance	not provided	2020-06-08	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003446269	SCV004172787	uncertain significance	Epilepsy, idiopathic generalized, susceptibility to, 12	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003446268	SCV004172788	uncertain significance	Dystonia 9	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003446266	SCV004172789	uncertain significance	Encephalopathy due to GLUT1 deficiency	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003446267	SCV004172790	uncertain significance	Childhood onset GLUT1 deficiency syndrome 2	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003446270	SCV004172791	uncertain significance	Hereditary cryohydrocytosis with reduced stomatin	2023-04-11	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001507437	SCV005433468	uncertain significance	not provided	2024-11-01	criteria provided, single submitter	clinical testing