ClinVar Miner

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

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000503047 SCV000594258 likely pathogenic Cerebroretinal microangiopathy with calcifications and cysts 2016-01-13 criteria provided, single submitter clinical testing
Invitae RCV000475703 SCV000541111 pathogenic Dyskeratosis congenita 2018-04-27 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.
OMIM RCV000033248 SCV000057104 pathogenic Cerebroretinal microangiopathy with calcifications and cysts 1 2012-08-01 no assertion criteria provided literature only

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