Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002563927 | SCV001411647 | uncertain significance | Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with phenylalanine at codon 434 of the TERT protein (p.Ser434Phe). The serine residue is weakly conserved and there is a large physicochemical difference between serine and phenylalanine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with TERT-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 | RCV004557478 | SCV002692491 | uncertain significance | Dyskeratosis congenita | 2022-10-02 | criteria provided, single submitter | clinical testing | The p.S434F variant (also known as c.1301C>T), located in coding exon 2 of the TERT gene, results from a C to T substitution at nucleotide position 1301. The serine at codon 434 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |