ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2303C>T (p.Pro768Leu)

dbSNP: rs1555506977
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000545258 SCV000644334 uncertain significance Tuberous sclerosis 2 2024-10-15 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 768 of the TSC2 protein (p.Pro768Leu). 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: 467933). 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.
Ambry Genetics RCV002448717 SCV002734875 uncertain significance Hereditary cancer-predisposing syndrome 2024-12-10 criteria provided, single submitter clinical testing The p.P768L variant (also known as c.2303C>T), located in coding exon 20 of the TSC2 gene, results from a C to T substitution at nucleotide position 2303. The proline at codon 768 is replaced by leucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
Baylor Genetics RCV004568831 SCV005054440 uncertain significance Isolated focal cortical dysplasia type II 2024-03-15 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005018945 SCV005645024 uncertain significance Lymphangiomyomatosis; Isolated focal cortical dysplasia type II; Tuberous sclerosis 2 2024-02-03 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004735611 SCV005357575 uncertain significance TSC2-related disorder 2024-08-24 no assertion criteria provided clinical testing The TSC2 c.2303C>T variant is predicted to result in the amino acid substitution p.Pro768Leu. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. This variant is interpreted as uncertain in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/467933/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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.