Submissions for variant NM_006516.4(SLC2A1):c.764A>C (p.Lys255Thr)

gnomAD frequency: 0.00013  dbSNP: rs5811

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000147532	SCV000194977	likely benign	not specified	2013-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001704070	SCV000242998	likely benign	not provided	2020-04-06	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24215330)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000805096	SCV000945040	uncertain significance	GLUT1 deficiency syndrome 1, autosomal recessive	2024-01-02	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 255 of the SLC2A1 protein (p.Lys255Thr). This variant is present in population databases (rs5811, gnomAD 0.02%). 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: 159929). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is not expected to disrupt SLC2A1 function with a negative predictive value of 80%. 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.
Illumina Laboratory Services, Illumina	RCV001096518	SCV001252737	uncertain significance	Encephalopathy due to GLUT1 deficiency	2018-01-15	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	RCV001096519	SCV001252738	uncertain significance	Dystonia 9	2018-01-15	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.
CeGaT Center for Human Genetics Tuebingen	RCV001704070	SCV002496866	uncertain significance	not provided	2024-01-01	criteria provided, single submitter	clinical testing	SLC2A1: PM2:Supporting
Ambry Genetics	RCV002390306	SCV002672834	likely benign	Inborn genetic diseases	2023-03-21	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.
Revvity Omics, Revvity	RCV001704070	SCV003825651	uncertain significance	not provided	2022-03-01	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV001704070	SCV004227814	uncertain significance	not provided	2023-02-24	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004737227	SCV005350512	likely benign	SLC2A1-related disorder	2024-08-09	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).