Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000545258 | SCV000644334 | uncertain significance | Tuberous sclerosis 2 | 2023-04-06 | 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: 467933). 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 proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 768 of the TSC2 protein (p.Pro768Leu). |
Ambry Genetics | RCV002448717 | SCV002734875 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-08 | criteria provided, single submitter | clinical testing | The p.P768L variant (also known as c.2303C>T), located in coding exon 20 of the TSC2 gene, results from a C to T substitution at nucleotide position 2303. The proline at codon 768 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |