ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.2995G>A (p.Gly999Arg) (rs780224196)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000570020 SCV000675374 uncertain significance Hereditary cancer-predisposing syndrome 2017-06-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727040 SCV000705103 uncertain significance not provided 2017-01-16 criteria provided, single submitter clinical testing
GeneDx RCV000727040 SCV000243509 uncertain significance not provided 2014-02-04 criteria provided, single submitter clinical testing p.Gly999Arg (GGG>AGG): c.2995 G>A in exon 23 of the TSC1 gene (NM_000368.4). The Gly999Arg missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a non-conservative amino acid substitution of an uncharged, non-polar Glycine residue with a positively charged, polar Arginine residue at a position that is conserved in the hamartin protein. In silico analysis is inconsistent with regard to the effect this variant may have on the protein structure/function. Additionally, the vast majority of TSC1 mutations result in protein truncation, while missense mutations have been reported only rarely (Northrup et al., 2011; Au et al., 2007). Therefore, based on the currently available information, it is unclear whether Gly999Arg is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).

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.