Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000190079 | SCV000243754 | uncertain significance | not provided | 2014-10-15 | criteria provided, single submitter | clinical testing | p.Arg1438Trp (CGG>TGG): c.4312 C>T in exon 34 of the TSC2 gene (NM_000548.3) A variant of unknown significance has been identified in the TSC2 gene. The R1438W variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. A different amino acid substitution at the same position (R1438Q) was reported as a de novo mutation in an individual with tuberous sclerosis (Roberts et al., 2004). R1438W was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R1438W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, the R1438W variant alters a poorly conserved position in the protein. Additionally, it is not within any known functional domain of the tuberin protein, where many pathogenic missense mutations have been identified (Northrup et al., 2011; Au et al., 2007). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSY panel(s). |
| Invitae | RCV000695662 | SCV000824176 | benign | Tuberous sclerosis 2 | 2023-12-15 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001022271 | SCV001183986 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-09 | criteria provided, single submitter | clinical testing | The p.R1438W variant (also known as c.4312C>T), located in coding exon 33 of the TSC2 gene, results from a C to T substitution at nucleotide position 4312. The arginine at codon 1438 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis.Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Genome- |
RCV000695662 | SCV002040821 | uncertain significance | Tuberous sclerosis 2 | 2021-11-07 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003462296 | SCV004205117 | uncertain significance | Isolated focal cortical dysplasia type II | 2022-08-23 | criteria provided, single submitter | clinical testing |