Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001046702 | SCV001210616 | uncertain significance | Tuberous sclerosis 1 | 2020-02-26 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with TSC1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 430 of the TSC1 protein (p.Pro430Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. |
| Ambry Genetics | RCV002379529 | SCV002690842 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-04 | criteria provided, single submitter | clinical testing | The p.P430L variant (also known as c.1289C>T), located in coding exon 11 of the TSC1 gene, results from a C to T substitution at nucleotide position 1289. The proline at codon 430 is replaced by leucine, 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. |