Submissions for variant NM_006516.4(SLC2A1):c.73C>A (p.Gln25Lys)

dbSNP: rs1165759782

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000820791	SCV000961519	uncertain significance	GLUT1 deficiency syndrome 1, autosomal recessive	2022-12-06	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) performed at Invitae indicates that this missense variant is expected to disrupt SLC2A1 protein function. ClinVar contains an entry for this variant (Variation ID: 663015). This variant has not been reported in the literature in individuals affected with SLC2A1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 25 of the SLC2A1 protein (p.Gln25Lys).
Mayo Clinic Laboratories, Mayo Clinic	RCV001507439	SCV001712992	uncertain significance	not provided	2020-07-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003317384	SCV004021052	uncertain significance	not specified	2023-06-14	criteria provided, single submitter	clinical testing	Variant summary: SLC2A1 c.73C>A (p.Gln25Lys) results in a conservative amino acid change located in the Major facilitator superfamily domain (IPR020846) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250478 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.73C>A has been reported in the literature in individuals affected with GLUT1 Deficiency Syndrome 1 and no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 35586607). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Genome-Nilou Lab	RCV003446458	SCV004173960	uncertain significance	Epilepsy, idiopathic generalized, susceptibility to, 12	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003446457	SCV004173961	uncertain significance	Dystonia 9	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003446455	SCV004173963	uncertain significance	Encephalopathy due to GLUT1 deficiency	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003446456	SCV004173964	uncertain significance	Childhood onset GLUT1 deficiency syndrome 2	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003446459	SCV004173965	uncertain significance	Hereditary cryohydrocytosis with reduced stomatin	2023-04-11	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004029048	SCV004949251	uncertain significance	Inborn genetic diseases	2024-01-25	criteria provided, single submitter	clinical testing	The c.73C>A (p.Q25K) alteration is located in exon 2 (coding exon 2) of the SLC2A1 gene. This alteration results from a C to A substitution at nucleotide position 73, causing the glutamine (Q) at amino acid position 25 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.