Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001019663 | SCV001181050 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-08-30 | criteria provided, single submitter | clinical testing | The c.3285-3C>A intronic variant results from a C to A substitution 3 nucleotides upstream from coding exon 28 in the TSC2 gene. This nucleotide position is poorly conserved in available vertebrate species. The BDGP splice prediction software does not produce a reliable prediction for the nearby native splice acceptor site, while the ESEfinder splice prediction software predicts a weakening in the native splice acceptor site efficiency; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV001206068 | SCV001377356 | uncertain significance | Tuberous sclerosis 2 | 2023-11-17 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 28 of the TSC2 gene. It does not directly change the encoded amino acid sequence of the TSC2 protein. It affects a nucleotide within the consensus splice site. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with TSC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 823429). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Genome- |
RCV001206068 | SCV002040758 | uncertain significance | Tuberous sclerosis 2 | 2021-11-07 | criteria provided, single submitter | clinical testing |