Description
The TSC2 c.4662G>C variant is predicted to result in the amino acid substitution p.Gln1554His. This variant occurs at the final nucleotide position of exon 36 and splicing prediction programs predict a splicing defect at the consensus donor site (SpliceAI, Jaganathan K, et al. 2019. PubMed ID: 30661751). This variant was reported as probably pathogenic in an individual with suspected tuberous sclerosis complex (TSC); however, detailed clinical information was not provided (Table S2, Hoogeveen-Westerveld et al. 2013. PubMed ID: 22903760). In addition, functional analyses of this variant showed that it led to an increased but "intermediate" effect when compared to wild type and a known pathogenic TSC2 variant (Table S1, Hoogeveen-Westerveld et al. 2013. PubMed ID: 22903760). This variant has not been reported in large population database, indicating this variant is rare. Of note, a different nucleotide variant (c.4662G>T) leading to the same amino acid change (p. Gln1554His) was reported as de novo in a patient with TSC (Rendtorff et al. 2005. PubMed ID: 16114042). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
