Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Prevention |
RCV003415784 | SCV004106210 | pathogenic | TSC2-related condition | 2023-09-27 | criteria provided, single submitter | clinical testing | The TSC2 c.911G>A variant is predicted to result in premature protein termination (p.Trp304*). This variant has been reported in individuals with tuberous sclerosis complex (Table 4, Dabora et al. 2001. PubMed ID: 11112665; Table S2, Martin et al. 2017. PubMed ID: 28643795; Table 2, Rosset et al. 2017. PubMed ID: 28968464). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. It is interpreted as pathogenic in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/49405/). Nonsense variants in TSC2 are expected to be pathogenic. This variant is interpreted as pathogenic. |
Tuberous sclerosis database |
RCV000042665 | SCV000066460 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation | ||
Genetic Services Laboratory, |
RCV003150939 | SCV003839178 | pathogenic | not provided | 2022-08-31 | no assertion criteria provided | clinical testing | DNA sequence analysis of the TSC2 gene demonstrated a sequence change, c.911G>A, which results in the creation of a premature stop codon at amino acid position 304, p.Trp304*. This pathogenic sequence change is predicted to result in an abnormal transcript, which may be degraded, or may lead to the production of a truncated TSC2 protein with potentially abnormal function. This sequence change has not been described in the population databases such as ExAC and gnomAD. This pathogenic sequence change has previously been described in individuals with TSC2-related disorders (PMID: 28643795, 28968464, 25782670). Collectively, these evidences indicate this sequence change is pathogenic. |