Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002563984 | SCV001413826 | uncertain significance | Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis | 2022-01-18 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 966224). This variant has not been reported in the literature in individuals affected with TERT-related conditions. This variant is present in population databases (rs745806589, gnomAD 0.003%). This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 550 of the TERT protein (p.Ser550Arg). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TERT 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 | RCV004557480 | SCV005049070 | uncertain significance | Dyskeratosis congenita | 2024-02-02 | criteria provided, single submitter | clinical testing | The p.S550R variant (also known as c.1648A>C), located in coding exon 3 of the TERT gene, results from an A to C substitution at nucleotide position 1648. The serine at codon 550 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |