ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.3289C>T (p.Arg1097Cys) (rs779599439)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189863 SCV000243516 uncertain significance not provided 2013-08-29 criteria provided, single submitter clinical testing p.Arg1097Cys (CGT>TGT): c.3289 C>T in exon 23 of the TSC1 gene (NM_000368.4). The Arg1097Cys 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. A different variant at the same position (Arg1097His) has been previously reported in an individual with clinical features of TSC; however, the variant was also identified in an unaffected parent (Nellist et al., 2009). The Arg1097Cys variant is a non-conservative amino acid substitution of a positively charged Arginine residue with an uncharged Cysteine residue, and the addition of a Cysteine residue may affect disulfide bonds and the secondary structure of the protein. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, the variant occurs at a position that is not highly conserved across species. 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 Arg1097Cys is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).
Invitae RCV000189863 SCV000552358 likely benign not provided 2019-02-12 criteria provided, single submitter clinical testing

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.