Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002564118 | SCV001420652 | uncertain significance | Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis | 2021-05-13 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with TERT-related conditions. 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 sequence change replaces proline with arginine at codon 445 of the TERT protein (p.Pro445Arg). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and arginine. 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 | RCV004557488 | SCV005049024 | likely benign | Dyskeratosis congenita | 2023-01-16 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Prevention |
RCV004545150 | SCV004800426 | uncertain significance | TERT-related disorder | 2024-02-28 | no assertion criteria provided | clinical testing | The TERT c.1334C>G variant is predicted to result in the amino acid substitution p.Pro445Arg. 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. This variant is interpreted as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/971459/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |