Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002533391 | SCV000770741 | uncertain significance | Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with glutamic acid at codon 398 of the TERT protein (p.Gly398Glu). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with TERT-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Ambry Genetics | RCV004559291 | SCV002644688 | uncertain significance | Dyskeratosis congenita | 2022-02-17 | criteria provided, single submitter | clinical testing | The p.G398E variant (also known as c.1193G>A), located in coding exon 2 of the TERT gene, results from a G to A substitution at nucleotide position 1193. The glycine at codon 398 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is conserved. 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. |
| Gene |
RCV004777801 | SCV005390315 | uncertain significance | not provided | 2024-04-22 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |