Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001212394 | SCV001383977 | uncertain significance | Tuberous sclerosis 2 | 2023-08-01 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 942410). 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 aspartic acid, which is acidic and polar, at codon 1565 of the TSC2 protein (p.Glu1565Asp). |
| Ambry Genetics | RCV002339550 | SCV002637825 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-19 | criteria provided, single submitter | clinical testing | The p.E1565D variant (also known as c.4695G>C), located in coding exon 36 of the TSC2 gene, results from a G to C substitution at nucleotide position 4695. The glutamic acid at codon 1565 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. 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. |