ClinVar Miner

Submissions for variant NM_025099.6(CTC1):c.2951_2953GTT[1] (p.Cys985del) (rs199473679)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000475703 SCV000541111 pathogenic Dyskeratosis congenita 2020-01-07 criteria provided, single submitter clinical testing This sequence change deletes 3 nucleotides from exon 18 of the CTC1 mRNA (c.2954_2956delGTT). This leads to the deletion of 1 amino acid residue in the CTC1 protein (p.Cys985del) but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs199473679, ExAC 0.01%). This variant has been reported in individuals affected with Coats plus, dyskeratosis congenita, and cerebroretinal microangiopathy with calcifications and cysts. These individuals also carried a truncating CTC1 variant (PMID: 22267198, 22387016, 22532422, 22899577). ClinVar contains an entry for this variant (Variation ID: 40250). The amino acid residue affected by this variant is located at the C-terminal domain that interacts with STN1 and TEN1, which is required to form a CST complex responsible for telomere replication (PMID: 24115768). Experimental studies have shown that this variant alone disrupts telomeric DNA binding and reduces CST complex formation (PMID: 24115768, 23869908), but does not affect telomere length maintenance and telomere localization (PMID: 24115768, 23869908). Patient-derived blood samples carrying this variant were shown to have shortened telomeres (PMID: 22267198, 22532422). For these reasons, this variant has been classified as Pathogenic.
Genetic Services Laboratory,University of Chicago RCV000503047 SCV000594258 pathogenic Cerebroretinal microangiopathy with calcifications and cysts 2018-07-30 criteria provided, single submitter clinical testing
OMIM RCV000033248 SCV000057104 pathogenic Cerebroretinal microangiopathy with calcifications and cysts 1 2012-08-01 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.