Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| All of Us Research Program, |
RCV004014182 | SCV004843772 | uncertain significance | Tuberous sclerosis syndrome | 2023-11-20 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with valine at codon 1238 of the TSC2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TSC2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV004950780 | SCV005527909 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-10-25 | criteria provided, single submitter | clinical testing | The p.A1238V variant (also known as c.3713C>T), located in coding exon 30 of the TSC2 gene, results from a C to T substitution at nucleotide position 3713. The alanine at codon 1238 is replaced by valine, an amino acid with similar properties. This variant was reported in an individual with a clinical diagnosis of tuberous sclerosis complex based on criteria from the 2012 International Tuberous Sclerosis Complex Consensus Group (Sudarshan S et al. BMC Med Genet, 2019 Oct;20:164). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |