Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics | RCV000013215 | SCV000255882 | pathogenic | Tuberous sclerosis 2 | 2014-12-03 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000013215 | SCV003443062 | pathogenic | Tuberous sclerosis 2 | 2024-11-19 | 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 altered 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 produces a non-functional protein and/or introduces a premature termination codon (PMID: 19259131). 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. |
ARUP Laboratories, |
RCV005229783 | SCV005876121 | pathogenic | not provided | 2024-01-19 | criteria provided, single submitter | clinical testing | The TSC2 c.2355+2_2355+5del variant (rs137854250) is reported in the literature in individuals affected with tuberous sclerosis complex (Babol-Pokora 2021, Le Caignec 2009, Niida 1999, Rosset 2017). This variant is reported in ClinVar (Variation ID: 12406). This variant is also absent from the Genome Aggregation Database (v2.1.1), indicating it is not a common polymorphism. This variant disrupts the canonical splice donor site of intron 21, and in vitro functional analyses demonstrate novel cryptic donor splice site and the generation of a premature stop codon (Le Caignec 2009). Based on available information, this variant is considered to be pathogenic. References: Babol-Pokora K et al. A multistep approach to the genotype-phenotype analysis of Polish patients with tuberous sclerosis complex. Eur J Med Genet. 2021 Oct;64(10):104309. PMID: 34403804. Le Caignec C. Three independent mutations in the TSC2 gene in a family with tuberous sclerosis. Eur J Hum Genet. 2009 Sep;17(9):1165-70. PMID: 19259131. Niida Y et al. Analysis of both TSC1 and TSC2 for germline mutations in 126 unrelated patients with tuberous sclerosis. Hum Mutat. 1999;14(5):412-22. PMID: 10533067. Rosset C et al. Molecular analysis of TSC1 and TSC2 genes and phenotypic correlations in Brazilian families with tuberous sclerosis. PLoS One. 2017 Oct 2;12(10):e0185713. PMID: 28968464. |
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 |