Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002415491 | SCV002725838 | pathogenic | Hereditary cancer-predisposing syndrome | 2017-10-09 | criteria provided, single submitter | clinical testing | The c.2098-2A>G intronic pathogenic mutation results from an A to G substitution two nucleotides upstream from coding exon 19 in the TSC2 gene. This alteration has been reported in the literature in an individual with a clinical diagnosis of tuberous sclerosis complex (Cai Y et al. Urology, 2017 Mar;101:170.e1-170.e7). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation. |
| Invitae | RCV003155053 | SCV004296652 | pathogenic | Tuberous sclerosis 2 | 2023-06-14 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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: 49731). Disruption of this splice site has been observed in individual(s) with tuberous sclerosis complex (PMID: 20633017, 28065512). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 19 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). |
| Tuberous sclerosis database |
RCV000042996 | SCV000066794 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation | ||
| Institute Of Reproduction And Development, |
RCV003155053 | SCV003844089 | likely pathogenic | Tuberous sclerosis 2 | 2021-06-24 | no assertion criteria provided | research |