Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001210084 | SCV001381550 | uncertain significance | Tuberous sclerosis 2 | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with valine at codon 1578 of the TSC2 protein (p.Leu1578Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. 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: "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 | RCV003163596 | SCV003861807 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-08 | criteria provided, single submitter | clinical testing | The p.L1578V variant (also known as c.4732C>G), located in coding exon 36 of the TSC2 gene, results from a C to G substitution at nucleotide position 4732. The leucine at codon 1578 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |