ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.1814C>T (p.Pro605Leu)

dbSNP: rs1555505178
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000644098 SCV000765788 uncertain significance Tuberous sclerosis 2 2022-11-23 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 535880). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 605 of the TSC2 protein (p.Pro605Leu).
Ambry Genetics RCV001013286 SCV001173854 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-01 criteria provided, single submitter clinical testing The p.P605L variant (also known as c.1814C>T), located in coding exon 16 of the TSC2 gene, results from a C to T substitution at nucleotide position 1814. The proline at codon 605 is replaced by leucine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. 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.
Genome-Nilou Lab RCV000644098 SCV002040641 uncertain significance Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000644098 SCV004360872 uncertain significance Tuberous sclerosis 2 2023-05-17 criteria provided, single submitter clinical testing This missense variant replaces proline with leucine at codon 605 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 not been reported in individuals affected with TSC2-related disorders in the literature. 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.

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.