Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002518368 | SCV000291851 | uncertain significance | Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis | 2023-10-30 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 530 of the TERT protein (p.Pro530Leu). This variant is present in population databases (rs369539932, gnomAD 0.007%). This missense change has been observed in individual(s) with non-alcoholic steatohepatitis (NASH), dyskeratosis congenita (DKC), and autosomal recessive Hoyeraal Hreidarrson syndrome (HHS) (PMID: 21520173, 22664374, 23335200, 26024875). ClinVar contains an entry for this variant (Variation ID: 242218). 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%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on TERT function (PMID: 21520173, 23335200). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 | RCV004567768 | SCV005052974 | uncertain significance | Dyskeratosis congenita, autosomal dominant 2 | 2024-02-15 | criteria provided, single submitter | clinical testing |