Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001207908 | SCV001379276 | uncertain significance | Tuberous sclerosis 2 | 2023-05-23 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 938643). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces serine, which is neutral and polar, with tryptophan, which is neutral and slightly polar, at codon 1336 of the TSC2 protein (p.Ser1336Trp). |
| Ambry Genetics | RCV002375148 | SCV002625367 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-10 | criteria provided, single submitter | clinical testing | The p.S1336W variant (also known as c.4007C>G), located in coding exon 33 of the TSC2 gene, results from a C to G substitution at nucleotide position 4007. The serine at codon 1336 is replaced by tryptophan, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. 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. |
| Baylor Genetics | RCV003462695 | SCV004206842 | uncertain significance | Isolated focal cortical dysplasia type II | 2023-09-15 | criteria provided, single submitter | clinical testing |