Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001204707 | SCV001375925 | uncertain significance | Tuberous sclerosis 2 | 2023-12-05 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1728 of the TSC2 protein (p.Ser1728Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 935997). 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 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. |
| Ambry Genetics | RCV002339515 | SCV002643733 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-07 | criteria provided, single submitter | clinical testing | The p.S1728I variant (also known as c.5183G>T), located in coding exon 40 of the TSC2 gene, results from a G to T substitution at nucleotide position 5183. The serine at codon 1728 is replaced by isoleucine, an amino acid with dissimilar 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. |