ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2042T>C (p.Leu681Pro)

gnomAD frequency: 0.00001  dbSNP: rs878854079
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
Invitae RCV000822530 SCV000963339 uncertain significance Tuberous sclerosis 2 2023-08-04 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 681 of the TSC2 protein (p.Leu681Pro). 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: 664430). 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.
Fulgent Genetics, Fulgent Genetics RCV002487850 SCV002785531 uncertain significance Lymphangiomyomatosis; Isolated focal cortical dysplasia type II; Tuberous sclerosis 2 2022-05-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV003380754 SCV004098197 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-03 criteria provided, single submitter clinical testing The p.L681P variant (also known as c.2042T>C), located in coding exon 18 of the TSC2 gene, results from a T to C substitution at nucleotide position 2042. The leucine at codon 681 is replaced by proline, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration 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.