Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000568333 | SCV000664712 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-06-17 | criteria provided, single submitter | clinical testing | The c.2042-5A>G intronic pathogenic mutation results from an A to G substitution 5 nucleotides upstream from coding exon 15 in the TSC1 gene. This nucleotide position is highly conserved in available vertebrate species. This variant has been observed in individuals with a personal and/or family history that is consistent with tuberous sclerosis complex (Ambry internal data; Rosengren T et al. Sci Rep, 2020 Jun;10:9909; External communication). In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Based on the supporting evidence, this variant is interpreted as a disease-causing mutation. |
| Labcorp Genetics |
RCV001222573 | SCV001394678 | likely pathogenic | Tuberous sclerosis 1 | 2024-11-18 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 16 of the TSC1 gene. It does not directly change the encoded amino acid sequence of the TSC1 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or altered protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with tuberous sclerosis complex (internal data). ClinVar contains an entry for this variant (Variation ID: 48882). Studies have shown that this variant results in activation of a cryptic splice site, and produces a non-functional protein and/or introduces a premature termination codon (internal data). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Tuberous sclerosis database |
RCV000042133 | SCV000065918 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation | ||
| Genome- |
RCV001222573 | SCV002041275 | uncertain significance | Tuberous sclerosis 1 | 2021-11-07 | flagged submission | clinical testing |