Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ce |
RCV002293115 | SCV002586042 | uncertain significance | not provided | 2022-08-01 | criteria provided, single submitter | clinical testing | TERT: PM2:Supporting, PP2, BP4 |
| Ambry Genetics | RCV004558922 | SCV002708733 | uncertain significance | Dyskeratosis congenita | 2022-09-12 | criteria provided, single submitter | clinical testing | The p.R521H variant (also known as c.1562G>A), located in coding exon 2 of the TERT gene, results from a G to A substitution at nucleotide position 1562. The arginine at codon 521 is replaced by histidine, an amino acid with highly 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. |
| Labcorp Genetics |
RCV003774979 | SCV004576790 | uncertain significance | Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis | 2023-11-12 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 521 of the TERT protein (p.Arg521His). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with TERT-related conditions. ClinVar contains an entry for this variant (Variation ID: 1711599). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The histidine 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. |
| Baylor Genetics | RCV004572126 | SCV005052984 | uncertain significance | Dyskeratosis congenita, autosomal dominant 2 | 2023-12-20 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV002293115 | SCV005443556 | uncertain significance | not provided | 2024-07-05 | 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 |