Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics Inc | RCV000013215 | SCV000255882 | pathogenic | Tuberous sclerosis 2 | 2014-12-03 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000013215 | SCV003443062 | pathogenic | Tuberous sclerosis 2 | 2023-09-27 | criteria provided, single submitter | clinical testing | This sequence change affects a splice site in intron 21 of the TSC2 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with Tuberous sclerosis (PMID: 10205261, 10533067, 19259131). In at least one individual the variant was observed to be de novo. This variant is also known as 2355+2delTAGG, c.2355+1_2355+4del, IVS20 + 1-4 delGTAG, 2373+2del4bp. ClinVar contains an entry for this variant (Variation ID: 12406). Studies have shown that disruption of this splice site results in activation of a cryptic splice site and introduces a premature termination codon (PMID: 19259131). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. |
| Illumina Laboratory Services, |
RCV000013215 | SCV004101301 | pathogenic | Tuberous sclerosis 2 | 2023-07-27 | criteria provided, single submitter | clinical testing | The TSC2 c.2355+2_2355+5del variant results in a deletion at the consensus splice donor site, which may result in splicing defects. This variant has been identified in at least five unrelated individuals with a phenotype consistent with tuberous sclerosis complex, including in one in which it occurred de novo (PMID: 10205261; 10533067; 19259131; 28968464; 34403804). This variant is not observed in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database. PCR analysis of cDNA from a patient with the c.2355+2_2355+5del variant demonstrated aberrant splicing that resulted in a premature stop codon (PMID: 19259131). Based on the available evidence, the c.2355+2_2355+5del variant is classified as pathogenic for tuberous sclerosis. |
| OMIM | RCV000013215 | SCV000033462 | pathogenic | Tuberous sclerosis 2 | 2009-09-01 | no assertion criteria provided | literature only | |
| Tuberous sclerosis database |
RCV000042461 | SCV000066252 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation | ||
| Tuberous sclerosis database |
RCV000042461 | SCV000066773 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation |