Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000644240 | SCV000765931 | pathogenic | Tuberous sclerosis 2 | 2020-06-03 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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). This sequence change affects a donor splice site in intron 37 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). This variant has been observed in individual(s) with clinical features of tuberous sclerosis complex (PMID: 17304050, Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 49864). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. |
| Ambry Genetics | RCV002336161 | SCV002639433 | pathogenic | Hereditary cancer-predisposing syndrome | 2017-05-26 | criteria provided, single submitter | clinical testing | The c.4849+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 36 of the TSC2 gene. This alteration was detected as a de novo occurrence in an individual with a clinical diagnosis of tuberous sclerosis complex (TSC) (Au KS et al. Genet. Med., 2007 Feb;9:88-100). In addition to the clinical data presented in the literature, since 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. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| Tuberous sclerosis database |
RCV000043130 | SCV000066929 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation |