ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.1258G>T (p.Glu420Ter)

dbSNP: rs796053484
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189977 SCV000243648 pathogenic not provided 2020-04-22 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Reliable data are not available in large population cohorts to assess the frequency of this variant in publicly available databases; however, this variant has not been detected in presumably healthy individuals tested at GeneDx.; This variant is associated with the following publications: (PMID: 29655203)
Labcorp Genetics (formerly Invitae), Labcorp RCV001051912 SCV001216094 pathogenic Tuberous sclerosis 2 2019-12-11 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in TSC2 are known to be pathogenic (PMID: 10205261, 17304050). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in individual(s) with clinical features of epilepsy and neurodevelopmental disorders (PMID: 29655203). ClinVar contains an entry for this variant (Variation ID: 207712). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu420*) in the TSC2 gene. It is expected to result in an absent or disrupted protein product.
Genome-Nilou Lab RCV001051912 SCV002040933 pathogenic Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001051912 SCV004360857 pathogenic Tuberous sclerosis 2 2022-10-12 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 13 of the TSC2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been reported in individuals affected with tuberous sclerosis complex in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of TSC2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
All of Us Research Program, National Institutes of Health RCV003996881 SCV004834017 pathogenic Tuberous sclerosis syndrome 2023-07-19 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 13 of the TSC2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been reported in individuals affected with tuberous sclerosis complex in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of TSC2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

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.