Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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- |
RCV000688940 | SCV002040755 | uncertain significance | Tuberous sclerosis 2 | 2021-11-07 | criteria provided, single submitter | clinical testing |