Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001379717 | SCV001577566 | likely pathogenic | Tuberous sclerosis 2 | 2020-01-07 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.Val184 amino acid residue in TSC2. Other variant(s) that disrupt this residue have been observed in individuals with TSC2-related conditions (Invitae), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with clinical features of tuberous sclerosis complex (PMID: 31140686). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with aspartic acid at codon 184 of the TSC2 protein (p.Val184Asp). The valine residue is highly conserved and there is a large physicochemical difference between valine and aspartic acid. |