Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002562550 | SCV001394322 | uncertain significance | Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with serine at codon 691 of the TERT protein (p.Arg691Ser). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and serine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |
Prevention |
RCV004528423 | SCV004105046 | uncertain significance | TERT-related disorder | 2023-07-28 | criteria provided, single submitter | clinical testing | The TERT c.2071C>A variant is predicted to result in the amino acid substitution p.Arg691Ser. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/950507/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Ambry Genetics | RCV004557439 | SCV005049103 | uncertain significance | Dyskeratosis congenita | 2023-06-11 | criteria provided, single submitter | clinical testing | The p.R691S variant (also known as c.2071C>A), located in coding exon 5 of the TERT gene, results from a C to A substitution at nucleotide position 2071. The arginine at codon 691 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |