ClinVar Miner

Submissions for variant NM_006516.4(SLC2A1):c.1396G>A (p.Gly466Ser)

gnomAD frequency: 0.00004  dbSNP: rs138139624
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766834 SCV000243018 uncertain significance not provided 2016-08-17 criteria provided, single submitter clinical testing p.Gly466Ser (GGC>AGC): c.1396 G>A in exon 10 of the SLC2A1 gene (NM_006516.2)A variant of unknown significance has been identified in the SLC2A1 gene. The G466S variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The G466S variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The G466S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution alters a conserved position in the C-terminal cytoplasmic region of the SLC2A1 protein (Wang et al., 2000); however, Serine is observed at this position in one species in distant evolution. Missense mutations in nearby residues (R458W, R468W) have been reported in association with SLC2A1-related disorders, supporting the functional importance of this region of the protein. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).
Genetic Services Laboratory, University of Chicago RCV000189380 SCV000597089 uncertain significance not specified 2015-11-09 criteria provided, single submitter clinical testing
Athena Diagnostics RCV000766834 SCV000615316 uncertain significance not provided 2019-01-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001049565 SCV001213622 uncertain significance GLUT1 deficiency syndrome 1, autosomal recessive 2024-12-16 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 466 of the SLC2A1 protein (p.Gly466Ser). This variant is present in population databases (rs138139624, gnomAD 0.007%). 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: 207214). 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.
CeGaT Center for Human Genetics Tuebingen RCV000766834 SCV001748135 uncertain significance not provided 2023-11-01 criteria provided, single submitter clinical testing SLC2A1: PM2
Genome-Nilou Lab RCV003445666 SCV004172269 uncertain significance Epilepsy, idiopathic generalized, susceptibility to, 12 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003445665 SCV004172270 uncertain significance Dystonia 9 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003445663 SCV004172271 uncertain significance Encephalopathy due to GLUT1 deficiency 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003445664 SCV004172273 uncertain significance Childhood onset GLUT1 deficiency syndrome 2 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003445667 SCV004172274 uncertain significance Hereditary cryohydrocytosis with reduced stomatin 2023-04-11 criteria provided, single submitter clinical testing

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