ClinVar Miner

Submissions for variant NM_198253.3(TERT):c.2146G>A (p.Ala716Thr)

dbSNP: rs387907249
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000030629 SCV000597466 pathogenic Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 2015-11-19 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000030629 SCV001429278 pathogenic Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 2019-08-23 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002513272 SCV003525636 pathogenic Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis 2024-03-26 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 716 of the TERT protein (p.Ala716Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with TERT-related conditions (PMID: 21436073, 30203795, 31268371). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 36948). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TERT protein function with a positive predictive value of 95%. This variant disrupts the p.Ala716 amino acid residue in TERT. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18931339, 21931702, 29146883; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Genetics and Molecular Pathology, SA Pathology RCV003447479 SCV004175571 likely pathogenic Dyskeratosis congenita, autosomal dominant 2 2021-07-22 criteria provided, single submitter clinical testing
OMIM RCV000030629 SCV000053307 pathogenic Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 2011-05-26 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.