ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.5220G>A (p.Trp1740Ter) (rs45517411)

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
GeneDx RCV000493371 SCV000583283 pathogenic not provided 2017-05-25 criteria provided, single submitter clinical testing The W1740X nonsense variant in the TSC2 gene has been reported previously as a de novo change in an individual with TSC (Roberts et al., 2002; TSC2 LOVD). This pathogenic variant is predicted to cause loss of normal protein function through protein truncation as the last 68 amino acids of the TSC2 protein are lost. The W1740X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).
Invitae RCV000802438 SCV000942270 pathogenic Tuberous sclerosis 2 2019-02-05 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the TSC2 gene (p.Trp1740*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 68 amino acids of the TSC2 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with tuberous sclerosis complex (PMID: 25782670, 12136241). ClinVar contains an entry for this variant (Variation ID: 49363). This variant disrupts the C-terminus of the TSC2 protein. Multiple frameshift variants including c.5340_5371del (p.1784Alafs*) and c.5405_5408dup (p.Phe1803Leufs*42), located downstream of this variant have been reported as disease-causing de novo variants in individuals affected with TSC (PMID: 10205261, 9328481, 24789117), suggesting that frameshift variants affecting the very C-terminal of TSC2 impact protein function and cause disease. For these reasons, this variant has been classified as Pathogenic.
Tuberous sclerosis database (TSC2) RCV000042623 SCV000066417 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.