Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000493895 | SCV000582857 | pathogenic | not provided | 2017-05-17 | criteria provided, single submitter | clinical testing | The W167X pathogenic variant in the TSC2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The W167X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret W167X as a pathogenic variant. |
| Invitae | RCV001050966 | SCV001215099 | pathogenic | Tuberous sclerosis 2 | 2021-06-28 | criteria provided, single submitter | clinical testing | This variant has been observed to be de novo in an individual affected with tuberoius sclerosis complex (PMID: 27859028). ClinVar contains an entry for this variant (Variation ID: 430129). For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in TSC2 are known to be pathogenic (PMID: 10205261, 17304050). A different variant (c.501G>A) giving rise to the same protein effect observed here (p.Trp167*) has been determined to be pathogenic (PMID:24668795, 28643795). This suggests that this variant is also likely to be causative of disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Trp167*) in the TSC2 gene. It is expected to result in an absent or disrupted protein product. |
| Genome- |
RCV001050966 | SCV002040916 | pathogenic | Tuberous sclerosis 2 | 2021-11-07 | criteria provided, single submitter | clinical testing |