ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.1864C>T (p.Arg622Trp) (rs397514914)

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 RCV000574001 SCV000675786 pathogenic Hereditary cancer-predisposing syndrome 2017-07-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Deficient protein function in appropriate functional assay(s),Good segregation with disease (lod 1.5-3 = 5-9 meioses),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Rarity in general population databases (dbsnp, esp, 1000 genomes)
Invitae RCV000644057 SCV000765747 uncertain significance Tuberous sclerosis 2 2017-09-13 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 622 of the TSC2 protein (p.Arg622Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with tuberous sclerosis (PMID: 28211972); several individuals affected with features of tuberous sclerosis (PMID: 21846442, 28211972, 21520333), but do not fulfill the established clinical criteria (PMID: 9881533); and their unaffected family members (PMID: 28211972, 21520333). This variant has also been reported in an individual affected with epilepsy (PMID: 22867869). ClinVar contains an entry for this variant (Variation ID: 64889). Experimental studies have shown that this missense change affects the ability of the TSC2 protein to form a complex with the TSC1 protein. This impairs the ability of the complex to regulate the mTOR signaling pathway (PMID: 21309039, 20633017). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Tuberous sclerosis database (TSC2) RCV000055090 SCV000083308 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.