ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.440C>A (p.Thr147Lys)

dbSNP: rs1555497690
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000644114 SCV000765804 likely pathogenic Tuberous sclerosis 2 2018-03-05 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). A different missense substitution at this codon (p.Thr147Arg) has been reported in an individual affected with tuberous sclerosis (PMID: 27859028). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been reported to be de novo in an individual affected with tuberous sclerosis (Invitae). This sequence change replaces threonine with lysine at codon 147 of the TSC2 protein (p.Thr147Lys). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and lysine.

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.