Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003797307 | SCV004588202 | uncertain significance | Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis | 2023-10-23 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 973 of the TERT protein (p.Lys973Thr). This variant is not present in population databases (gnomAD 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 with a positive predictive value of 95%. 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 | RCV004823225 | SCV005512458 | uncertain significance | Dyskeratosis congenita | 2024-10-18 | criteria provided, single submitter | clinical testing | The p.K973T variant (also known as c.2918A>C), located in coding exon 12 of the TERT gene, results from an A to C substitution at nucleotide position 2918. The lysine at codon 973 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 variant remains unclear. |