Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000473316 | SCV000544408 | likely pathogenic | Tuberous sclerosis 2 | 2016-07-14 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with cysteine at codon 598 of the TSC2 protein (p.Tyr598Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with tuberous sclerosis complex (TSC) in the literature and in the Leiden Open-source Variation Database (PMID: 21520333, 22903760). ClinVar contains an entry for this variant (Variation ID: 50162). An experimental study has shown that this missense change disrupts the protein-protein interactions and activity of the TSC2 protein in cell culture (PMID: 22903760). A different missense substitution at this codon (p.Tyr598His) has been determined to be likely pathogenic (PMID: 21520333, 21309039). This suggests that the tyrosine residue is critical for TSC2 protein function and that other missense substitutions at this position may also be pathogenic. In summary, this is a rare missense variant that likely disrupts protein function and has been observed in affected individuals. However, without additional functional studies or segregation data, this variant has been classified as Likely Pathogenic. |
| Tuberous sclerosis database |
RCV000043430 | SCV000067236 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation |