Submissions for variant NM_006516.4(SLC2A1):c.313G>A (p.Val105Met)

gnomAD frequency: 0.00003  dbSNP: rs577667739

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001721221	SCV000242986	likely benign	not provided	2019-05-24	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000346798	SCV000357705	uncertain significance	Encephalopathy due to GLUT1 deficiency	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000394308	SCV000357706	uncertain significance	Dystonia 9	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV000468529	SCV000545830	uncertain significance	GLUT1 deficiency syndrome 1, autosomal recessive	2023-10-24	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 105 of the SLC2A1 protein (p.Val105Met). This variant is present in population databases (rs577667739, gnomAD 0.008%). 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: 207189). 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 not expected to disrupt SLC2A1 protein 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.
Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn	RCV003326127	SCV004032490	uncertain significance	Hereditary cryohydrocytosis with reduced stomatin; Encephalopathy due to GLUT1 deficiency; Childhood onset GLUT1 deficiency syndrome 2; Epilepsy, idiopathic generalized, susceptibility to, 12	2023-04-13	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004553027	SCV004781354	uncertain significance	SLC2A1-related disorder	2023-12-27	criteria provided, single submitter	clinical testing	The SLC2A1 c.313G>A variant is predicted to result in the amino acid substitution p.Val105Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0080% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.