Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001919946 | SCV002165808 | benign | Tuberous sclerosis 2 | 2025-01-28 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV002291783 | SCV002584452 | uncertain significance | not provided | 2024-04-14 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in a patient with clinically suspected tuberous sclerosis complex, and was reported to be paternally inherited (PMID: 32917966); This variant is associated with the following publications: (PMID: 18466115, 32917966) |
| Ambry Genetics | RCV002334833 | SCV002641275 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-11-14 | criteria provided, single submitter | clinical testing | The p.V1683L variant (also known as c.5047G>C), located in coding exon 38 of the TSC2 gene, results from a G to C substitution at nucleotide position 5047. The valine at codon 1683 is replaced by leucine, an amino acid with highly similar properties. This alteration has been reported in an individual with cortical dysplasias and epilepsy, in conjunction with TSC2 p.V892F (Meng Y et al. J Hum Genet, 2021 Mar;66:227-236). This amino acid position is not well conserved in available vertebrate species, and leucine is the reference amino acid in other 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. |
| All of Us Research Program, |
RCV004010800 | SCV004840723 | uncertain significance | Tuberous sclerosis syndrome | 2023-12-18 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with leucine at codon 1683 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 been reported in an individual with suspected tuberous sclerosis complex (PMID: 32917966) . 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. |