Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000799456 | SCV000939119 | uncertain significance | Tuberous sclerosis 2 | 2018-10-08 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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"). 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 valine at codon 205 of the TSC2 protein (p.Leu205Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. |
Ambry Genetics | RCV002352348 | SCV002657035 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-02 | criteria provided, single submitter | clinical testing | The p.L205V variant (also known as c.613C>G), located in coding exon 6 of the TSC2 gene, results from a C to G substitution at nucleotide position 613. The leucine at codon 205 is replaced by valine, an amino acid with highly 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. |