ClinVar Miner

Submissions for variant NM_001363.5(DKC1):c.1223C>T (p.Thr408Ile)

dbSNP: rs199422254
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255428 SCV000321554 likely pathogenic not provided 2019-08-05 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 31269755, 20301779, 16332973)
Invitae RCV001048156 SCV001212146 uncertain significance Dyskeratosis congenita 2020-01-19 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individuals affected with dyskeratosis congenita (PMID: 16332973, Invitae). ClinVar contains an entry for this variant (Variation ID: 38941). This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with isoleucine at codon 408 of the DKC1 protein (p.Thr408Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine.
Genetic Services Laboratory, University of Chicago RCV000255428 SCV002067418 likely pathogenic not provided 2019-11-15 criteria provided, single submitter clinical testing
GeneReviews RCV000032192 SCV000055782 not provided Dyskeratosis congenita, X-linked no assertion 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.