Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000701173 | SCV000829959 | pathogenic | Tuberous sclerosis 2 | 2018-02-01 | criteria provided, single submitter | clinical testing | This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). Additionally, a different variant affecting this nucleotide (c.2743-1G>C, also reported as c.2761-1G>C) has been reported in an individual affected with tuberous sclerosis (PMID: 12111193).ClinVar contains an entry for this variant (Variation ID: 49560). This sequence change affects an acceptor splice site in intron 24 of the TSC2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Donor and acceptor splice site variants 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. |
| Ambry Genetics | RCV002433526 | SCV002747526 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-06-19 | criteria provided, single submitter | clinical testing | The c.2743-1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide upstream from coding exon 24 of the TSC2 gene. This mutation was identified in an individual with seizures, skin findings including hypomelanotic macules, facial angiofibromas, confetti like hypopigmented macules, and shagreen patches, adenoma sebaceum, and ungual fibromas. In addition, a cell line from this individual demonstrated radiosensitivity (Au KS et al. Genet. Med., 2007 Feb;9:88-100; Ferlazzo ML et al. Mol. Neurobiol., 2018 Jun;55:4973-4983). 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. |
| Tuberous sclerosis database |
RCV000042820 | SCV000066616 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation |