Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000551770 | SCV000650772 | uncertain significance | Interstitial lung disease 2; Dyskeratosis congenita, autosomal dominant 2 | 2020-10-25 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with methionine at codon 1090 of the TERT protein (p.Val1090Met). The valine residue is weakly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs121918664, ExAC 0.03%). This variant has been observed in an individual affected with aplastic anaemia, and an unrelated individual affected with hepatocellular carcinoma, but was also observed in one healthy individual (PMID: 15814878, 28813500 19561322). ClinVar contains an entry for this variant (Variation ID: 12733). Experimental studies using a cell model have shown that this variant results in a reduction of telomerase activity (PMID: 15814878, 23901009, 19561322, 26365799, 28813500, 28154186). 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. |
Mendelics | RCV000708946 | SCV000838054 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000987498 | SCV001136803 | uncertain significance | Interstitial lung disease 2 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
St. |
RCV002254676 | SCV002526099 | uncertain significance | Dyskeratosis congenita, autosomal dominant 2 | 2022-02-10 | criteria provided, single submitter | clinical testing | The TERT c.3268G>A (p.Val1090Met) missense change has a maximum subpopulation frequency of 0.024% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/5-1254510-C-T?dataset=gnomad_r2_1). This variant occurs in a gene where missense variants are more likely to be damaging based on methods described by Lek et al. (PP2; PMID: 27535533). In silico tools are not in agreement about the effect of this variant on protein function, but functional assays on this variant have shown telomere length shortening, reduced hematopoietic function and loss of telomerase activity (PS3; PMID: 15814878, 19796246, 26365799, 28154186). This variant has been observed in an individual with aplastic anemia (PMID: 15814878), hepatocellular carcinoma (PMID: 2881350) and one healthy carrier (PMID: 19561322). To our knowledge, this variant has not been reported in individuals with clinical features of dyskeratosis congenita. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: PS3, PP2. |
Fulgent Genetics, |
RCV002482862 | SCV002783581 | uncertain significance | Interstitial lung disease 2; Aplastic anemia; Dyskeratosis congenita, autosomal dominant 1; Acute myeloid leukemia; Dyskeratosis congenita, autosomal dominant 2; Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1; Melanoma, cutaneous malignant, susceptibility to, 9 | 2022-05-12 | criteria provided, single submitter | clinical testing | |
Gene |
RCV003226897 | SCV003923848 | uncertain significance | not provided | 2022-11-07 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect: reduced telomere length and elongation capacity, as well as reduced telomerase activity and telomerase processivity (Yamaguchi et al., 2005; Calado et al., 2009; Hoffman et al., 2017; Reilly et al., 2021); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 19796246, 19561322, 34019641, 28154186, 23901009, 26365799, 23538340, 20301779, 23716176, 16647572, 26851889, 28813500, 15814878) |
Baylor Genetics | RCV002254676 | SCV004208117 | uncertain significance | Dyskeratosis congenita, autosomal dominant 2 | 2023-09-25 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000013570 | SCV000033817 | pathogenic | Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 | 2005-04-07 | no assertion criteria provided | literature only | |
Gene |
RCV000032394 | SCV000056050 | not provided | Aplastic anemia | no assertion provided | literature only | ||
Genome |
RCV000551770 | SCV001749437 | not provided | Interstitial lung disease 2; Dyskeratosis congenita, autosomal dominant 2 | no assertion provided | phenotyping only | Variant interpreted as Uncertain significance and reported on 01-05-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. |