ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.656T>C (p.Leu219Pro)

dbSNP: rs397515249
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
Labcorp Genetics (formerly Invitae), Labcorp RCV001053191 SCV001217438 uncertain significance Tuberous sclerosis 2 2019-03-17 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 219 of the TSC2 protein (p.Leu219Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 65337). This variant has been reported to affect TSC2 protein function (PMID: 21309039). 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.
MGZ Medical Genetics Center RCV001053191 SCV002579265 pathogenic Tuberous sclerosis 2 2021-08-10 criteria provided, single submitter clinical testing
GeneDx RCV004700354 SCV005201227 pathogenic not provided 2023-11-28 criteria provided, single submitter clinical testing Functional studies demonstrate an impaired TSC1-TSC2 complex formation and impaired inhibition of mTOR activity (PMID: 21309039); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 18466115, 27493206, 32211034, 21309039)
Tuberous sclerosis database (TSC2) RCV000055561 SCV000083785 not provided Tuberous sclerosis syndrome no assertion provided curation

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.