Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001852890 | SCV002281684 | likely pathogenic | Tuberous sclerosis 2 | 2021-10-05 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 49518). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with cysteine at codon 1571 of the TSC2 protein (p.Tyr1571Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TSC2 protein function. 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.Tyr1571 amino acid residue in TSC2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11290735, 11521203, 12511557; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. |
| Tuberous sclerosis database |
RCV000042778 | SCV000066574 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation |