Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002560542 | SCV002199041 | uncertain significance | Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis | 2020-12-12 | criteria provided, single submitter | clinical testing | 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. 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. This variant has not been reported in the literature in individuals with TERT-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with serine at codon 403 of the TERT protein (p.Cys403Ser). The cysteine residue is highly conserved and there is a moderate physicochemical difference between cysteine and serine. |
| Ambry Genetics | RCV004558741 | SCV005048936 | uncertain significance | Dyskeratosis congenita | 2022-12-23 | criteria provided, single submitter | clinical testing | The p.C403S variant (also known as c.1208G>C), located in coding exon 2 of the TERT gene, results from a G to C substitution at nucleotide position 1208. The cysteine at codon 403 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |