Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001011147 | SCV001171436 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-10-24 | criteria provided, single submitter | clinical testing | The p.G452D variant (also known as c.1355G>A), located in coding exon 12 of the TSC1 gene, results from a G to A substitution at nucleotide position 1355. The glycine at codon 452 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is well 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. |
Invitae | RCV001219824 | SCV001391782 | uncertain significance | Tuberous sclerosis 1 | 2020-10-14 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with aspartic acid at codon 452 of the TSC1 protein (p.Gly452Asp). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is not present in population databases (ExAC no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with TSC1-related conditions. |
Genome- |
RCV001219824 | SCV002039253 | uncertain significance | Tuberous sclerosis 1 | 2021-11-07 | criteria provided, single submitter | clinical testing |