ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.5024C>A (p.Pro1675Gln) (rs45483392)

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
Invitae RCV000644091 SCV000765781 pathogenic Tuberous sclerosis 2 2018-03-01 criteria provided, single submitter clinical testing This sequence change replaces proline with glutamine at codon 1675 of the TSC2 protein (p.Pro1675Gln). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in individuals affected with tuberous sclerosis complex (PMID: 21520333, Invitae). 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"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. A different missense substitution at this codon (p.Pro1675Leu) has been determined to be pathogenic (PMID: 9302281, 22867869, 11520734, 9463313, 12111193, 15024740, 21520333). This suggests that the proline residue is critical for TSC2 protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.

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.