Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002551219 | SCV002310083 | uncertain significance | Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis | 2021-09-07 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with threonine at codon 699 of the TERT protein (p.Ala699Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. 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. 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 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 | RCV004558817 | SCV005049105 | uncertain significance | Dyskeratosis congenita | 2024-02-16 | criteria provided, single submitter | clinical testing | The p.A699T variant (also known as c.2095G>A), located in coding exon 5 of the TERT gene, results from a G to A substitution at nucleotide position 2095. The alanine at codon 699 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. |