Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000226898 | SCV000285342 | uncertain significance | Tuberous sclerosis 2 | 2022-10-05 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 238017). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. 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 alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 1116 of the TSC2 protein (p.Ala1116Gly). |
Ambry Genetics | RCV002321858 | SCV002606703 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-17 | criteria provided, single submitter | clinical testing | The p.A1116G variant (also known as c.3347C>G), located in coding exon 28 of the TSC2 gene, results from a C to G substitution at nucleotide position 3347. The alanine at codon 1116 is replaced by glycine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |