Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000695700 | SCV000824215 | uncertain significance | Tuberous sclerosis 2 | 2018-06-13 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with TSC2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 1423 of the TSC2 protein (p.Leu1423Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 | RCV003303149 | SCV003998259 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-17 | criteria provided, single submitter | clinical testing | The p.L1423P variant (also known as c.4268T>C), located in coding exon 33 of the TSC2 gene, results from a T to C substitution at nucleotide position 4268. The leucine at codon 1423 is replaced by proline, 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. |