ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3278A>G (p.Glu1093Gly)

dbSNP: rs796053494
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000190018 SCV000243690 uncertain significance not provided 2013-01-07 criteria provided, single submitter clinical testing p.Glu1093Gly (GAG>GGG): c.3278 A>G in exon 28 of the TSC2 gene (NM_000548.3)The Glu1093Gly missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Project has not identified Glu1093Gly in approximately 6,500 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. The amino acid substitution is non-conservative, as a negatively charged, polar Glutamic acid is replaced by an uncharged, non-polar Glycine residue. While other nearby missense mutations have been reported in association with tuberous sclerosis, Glu1093Gly does not occur within known functional domains of the protein, where many pathogenic missense mutations have been identified (Northrup et al., 2011; Au et al., 2007). In addition, Glu1093Gly alters a poorly conserved position in the tuberin protein and several in-silico algorithms predict it may be non-pathogenic. Therefore, based on the currently available information, it is unclear whether Glu1093Gly is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).
Invitae RCV000688940 SCV000816571 uncertain significance Tuberous sclerosis 2 2023-06-05 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 not expected to disrupt TSC2 protein function. ClinVar contains an entry for this variant (Variation ID: 207744). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1093 of the TSC2 protein (p.Glu1093Gly).
Genome-Nilou Lab RCV000688940 SCV002040755 uncertain significance Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.