Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000794666 | SCV000934087 | uncertain significance | Tuberous sclerosis 2 | 2018-07-15 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 proline with threonine at codon 541 of the TSC2 protein (p.Pro541Thr). The proline residue is weakly conserved and there is a small physicochemical difference between proline and threonine. |
| Ambry Genetics | RCV002397580 | SCV002708915 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-25 | criteria provided, single submitter | clinical testing | The p.P541T variant (also known as c.1621C>A), located in coding exon 15 of the TSC2 gene, results from a C to A substitution at nucleotide position 1621. The proline at codon 541 is replaced by threonine, an amino acid with highly similar properties. This amino acid position is not well 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. |