ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.1369T>A (p.Ser457Thr)

dbSNP: rs2151170866
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001995044 SCV002248072 uncertain significance Tuberous sclerosis 2 2024-08-27 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 457 of the TSC2 protein (p.Ser457Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1469768). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt TSC2 protein function with a negative predictive value of 95%. 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.
All of Us Research Program, National Institutes of Health RCV004011013 SCV004837663 uncertain significance Tuberous sclerosis syndrome 2023-11-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV004946954 SCV005527624 uncertain significance Hereditary cancer-predisposing syndrome 2024-11-07 criteria provided, single submitter clinical testing The p.S457T variant (also known as c.1369T>A), located in coding exon 13 of the TSC2 gene, results from a T to A substitution at nucleotide position 1369. The serine at codon 457 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.