Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000498860 | SCV000589551 | pathogenic | not provided | 2018-12-03 | criteria provided, single submitter | clinical testing | The c.1839+1 G>T splice site variant in the TSC2 gene has been reported multiple timespreviously reported in association with TSC (Crino et al., 2010; TSC2 LOVD). This pathogenic variant destroys the canonical splice donor site in intron 17, and is expected to cause abnormal gene splicing. The c.1839+1 G>T variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Therefore, the presence of c.1839+1 G>T is consistent with the diagnosis of TSC in this individual. |
| Invitae | RCV003512003 | SCV004296650 | pathogenic | Tuberous sclerosis 2 | 2022-11-24 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 50178). This variant is also known as IVS16+1G>T. Disruption of this splice site has been observed in individuals with tuberous sclerosis complex (PMID: 15798777, 18410267, 25782670; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 17 of the TSC2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TSC2 are known to be pathogenic (PMID: 10205261, 17304050). For these reasons, this variant has been classified as Pathogenic. |
| Tuberous sclerosis database |
RCV000043446 | SCV000067253 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation |