Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002530132 | SCV000650737 | uncertain significance | Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis | 2024-01-05 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 741 of the TERT protein (p.Val741Met). This variant is present in population databases (rs150819225, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with TERT-related conditions. ClinVar contains an entry for this variant (Variation ID: 471857). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Center for Genomics, |
RCV000768106 | SCV000899021 | uncertain significance | Acute myeloid leukemia; Dyskeratosis congenita, autosomal dominant 2; Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1; Melanoma, cutaneous malignant, susceptibility to, 9 | 2021-03-30 | criteria provided, single submitter | clinical testing | TERT NM_198253.2 exon 6 p.Val741Met (c.2221G>A): This variant has not been reported in the literature, but it is present in 3/24032 of African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/5-1278821-C-T). This variant is present in ClinVar (Variation ID: 471857). This variant amino acid, Methionine (Met), is present in three mammalian species (Gorilla, Pika, Panda) and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant are insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |
| Gene |
RCV001559069 | SCV001781140 | uncertain significance | not provided | 2023-08-02 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Identified in individuals with myeloid neoplasia (Gurnari et al., 2022); This variant is associated with the following publications: (PMID: 35106810) |
| Ambry Genetics | RCV004559190 | SCV002729690 | uncertain significance | Dyskeratosis congenita | 2022-02-12 | criteria provided, single submitter | clinical testing | The p.V741M variant (also known as c.2221G>A), located in coding exon 6 of the TERT gene, results from a G to A substitution at nucleotide position 2221. The valine at codon 741 is replaced by methionine, an amino acid with highly similar 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. |
| Baylor Genetics | RCV003470765 | SCV004208109 | uncertain significance | Dyskeratosis congenita, autosomal dominant 2 | 2024-02-13 | criteria provided, single submitter | clinical testing |