Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000491444 | SCV000579599 | pathogenic | Hereditary cancer-predisposing syndrome | 2016-06-24 | criteria provided, single submitter | clinical testing | The p.L850P pathogenic mutation (also known as c.2549T>C), located in coding exon 22 of the TSC2 gene, results from a T to C substitution at nucleotide position 2549. The leucine at codon 850 is replaced by proline, an amino acid with some similar properties. This alteration has been reported as de novo in a patient with tuberous sclerosis complex (Au KS et al, Genet. Med. 2007 Feb; 9(2):88-100). In another study, this mutation was also detected in an individual with tuberous sclerosis complex undergoing everolimus treatment for subependymal giant cell astrocytomas(Kwiatkowski DJ et al, Eur. J. Hum. Genet. 2015 Dec; 23(12):1665-72). Based on the available evidence, p.L850P is classified as a pathogenic mutation. |
| Invitae | RCV001852902 | SCV002282672 | likely pathogenic | Tuberous sclerosis 2 | 2021-07-14 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 50077). This variant has been observed in individuals with tuberous sclerosis complex (PMID: 17304050, 25782670; Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 850 of the TSC2 protein (p.Leu850Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. |
| Tuberous sclerosis database |
RCV000043343 | SCV000067149 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation |