ClinVar Miner

Submissions for variant NM_198253.3(TERT):c.2594G>A (p.Arg865His) (rs121918666)

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
GeneDx RCV000412959 SCV000490843 pathogenic not provided 2017-10-18 criteria provided, single submitter clinical testing The R865H variant has been published previously in association with TERT-related disorders (Tsakiri et al., 2007; Fernandez et al., 2012; DiNardo et al., 2016). The variant is observed in 1/23030 (0.004%) alleles from individuals of African background in the ExAC dataset (Lek et al., 2016). This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, functional studies have demonstrated that R865H results in significantly reduced enzyme activities (Tsakiri et al., 2007; Zaug et al., 2013). In summary, we consider this variant to be pathogenic.
Invitae RCV001233436 SCV001406029 uncertain significance Idiopathic Pulmonary Fibrosis; Dyskeratosis congenita, autosomal dominant, 2 2019-09-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 865 of the TERT protein (p.Arg865His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs121918666, ExAC 0.01%). This variant has been observed in families affected with idiopathic pulmonary fibrosis (PMID: 17460043, 22853774). This variant has also been observed in an individual affected with dyskeratosis congenita (PMID: 28102861). ClinVar contains an entry for this variant (Variation ID: 12736). This variant has been reported to affect TERT protein function (PMID: 17460043, 20022961, 22364217, 23901009, 25365545). 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.
OMIM RCV000013573 SCV000033820 pathogenic Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1 2007-05-01 no assertion criteria provided literature only
GeneReviews RCV000032385 SCV000056041 pathologic Idiopathic Pulmonary Fibrosis 2012-05-10 no assertion criteria provided curation Converted during submission to Pathogenic.
Department of Respiratory and Critical Care Medicine, Tongji Hospital,Tongji Medical College, Huazhong University of Science and Technology RCV000032385 SCV000803358 pathogenic Idiopathic Pulmonary Fibrosis 2018-05-06 no assertion criteria provided case-control

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.