Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000800422 | SCV000940137 | uncertain significance | Tuberous sclerosis 2 | 2019-10-24 | 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: "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 proline with serine at codon 824 of the TSC2 protein (p.Pro824Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003226395 | SCV003922736 | uncertain significance | not specified | 2023-03-03 | criteria provided, single submitter | clinical testing | Variant summary: TSC2 c.2470C>T (p.Pro824Ser) results in a non-conservative amino acid change located in the tuberin-type domain (IPR018515) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250532 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2470C>T in individuals affected with Tuberous Sclerosis Complex and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted a clinical-significance assessment for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |