Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001014862 | SCV001175627 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-02 | criteria provided, single submitter | clinical testing | The p.S758F variant (also known as c.2273C>T), located in coding exon 20 of the TSC2 gene, results from a C to T substitution at nucleotide position 2273. The serine at codon 758 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This variant was reported in 1/325 individuals with a clinical diagnosis of tuberous sclerosis complex; this patient did not have a known family history of tuberous sclerosis (Au KS et al. Genet. Med. 2007 Feb;9:88-100). This amino acid position is highly conserved in available 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. |
| Labcorp Genetics |
RCV003511989 | SCV004296653 | uncertain significance | Tuberous sclerosis 2 | 2023-04-12 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 758 of the TSC2 protein (p.Ser758Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with tuberous sclerosis complex (PMID: 17304050). ClinVar contains an entry for this variant (Variation ID: 49710). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TSC2 protein function. 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. |
| Tuberous sclerosis database |
RCV000042974 | SCV000066771 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation |