ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.1960C>T (p.Gln654Ter) (rs75820036)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000698745 SCV000827428 pathogenic Tuberous sclerosis 1 2018-07-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln654*) in the TSC1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with tuberous sclerosis complex (PMID: 9924605, 11112665, 23389244). The variant is also known as c.2181C>T (p.Q554X) in the literature. ClinVar contains an entry for this variant (Variation ID: 48858). Loss-of-function variants in TSC1 are known to be pathogenic (PMID: 10227394, 17304050). For these reasons, this variant has been classified as Pathogenic.
Athena Diagnostics Inc RCV000713908 SCV000844549 pathogenic not provided 2018-08-07 criteria provided, single submitter clinical testing
GeneDx RCV000713908 SCV000890241 pathogenic not provided 2018-11-26 criteria provided, single submitter clinical testing The Q654X nonsense variant in the TSC1 gene has been reported multiple times in association with tuberous sclerosis complex (Kwiatkowska et al., 1998; Dabora et al., 1998; Niida et al., 2013). The variant has been referred to as Q554X due to the use of alternative nomenclature. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Q654X variant is not observed in large population cohorts (Lek et al., 2016). GeneDx interprets Q654X as a pathogenic variant.
Tuberous sclerosis database (TSC1) RCV000042109 SCV000065894 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.