Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003645857 | SCV004450404 | likely pathogenic | Dyskeratosis congenita | 2023-11-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg1195*) in the CTC1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 23 amino acid(s) of the CTC1 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with cerebral microangiopathy with calcifications and cysts (PMID: 22387016). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as R1190*. ClinVar contains an entry for this variant (Variation ID: 31003). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects CTC1 function (PMID: 23869908). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| OMIM | RCV000023994 | SCV000045285 | pathogenic | Cerebroretinal microangiopathy with calcifications and cysts 1 | 2012-03-09 | no assertion criteria provided | literature only |