Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001086904 | SCV000544331 | likely benign | Tuberous sclerosis 2 | 2024-01-05 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002255384 | SCV000847588 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-25 | criteria provided, single submitter | clinical testing | The p.R308W variant (also known as c.922C>T), located in coding exon 9 of the TSC2 gene, results from a C to T substitution at nucleotide position 922. The arginine at codon 308 is replaced by tryptophan, an amino acid with dissimilar properties. One study reports that this alteration has been identified in multiple individuals with phenotypes consistent with tuberous sclerosis (Dufner Almeida LG et al. Hum Mutat. 2020 04;41(4):759-773). However, this variant has also been detected in multiple individuals with no reported features of TSC2-associated disease (Ambry internal data). A functional study indicated that this alteration results in impaired binding with TSC1 and slightly increased phosphorylation of S6K on residue T389, however the authors also noted that the clinical significance of these findings was not clear since the variant had been reported in both patients meeting clinical criteria for tuberous sclerosis and unaffected individuals (Dufner Almeida LG et al. Hum Mutat. 2020 04;41(4):759-773). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is conflicting at this time, the clinical significance of this alteration remains unclear. |
Eurofins Ntd Llc |
RCV000732320 | SCV000860255 | uncertain significance | not provided | 2018-03-27 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000732320 | SCV001805768 | uncertain significance | not provided | 2023-02-27 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect as R308W interfered with TSC1 binding and disrupted the TSC complex function (Dufner Almeida et al., 2020); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29432982, 27149507, 31799751, 34403804, 18466115) |
Genome- |
RCV001086904 | SCV002041114 | uncertain significance | Tuberous sclerosis 2 | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV002255384 | SCV002534124 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-10 | criteria provided, single submitter | curation |