Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000023993 | SCV003844293 | likely pathogenic | Cerebroretinal microangiopathy with calcifications and cysts 1 | 2023-02-27 | criteria provided, single submitter | clinical testing | Variant summary: CTC1 c.1994T>G (p.Val665Gly) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0002 in 249480 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in CTC1 causing Cerebroretinal Microangiopathy With Calcifications And Cysts 1 (0.0002 vs 0.0011), allowing no conclusion about variant significance. However, it has been observed primarily within the Finnish subpopulation in the gnomAD database at a frequency of 0.0022, suggesting it could possibly be a benign polymorphism found predominantly within individuals of Finnish ancestry. c.1994T>G has been reported in the literature in multiple individuals affected with Cerebroretinal Microangiopathy With Calcifications And Cysts (CRMCC), including cases where it has been confirmed to be in trans with a pathogenic variant and in families where it has segregated with the disease phenotype (e.g. Polvi_2012, Mansukhani_2017). These data indicate that the variant is likely to be associated with disease. Publications report experimental evidence suggesting that the variant has an impact on protein function, reducing telomere association and impairing response to replication stress (e.g. Chen_2013, Wang_2018). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Gene |
RCV003227608 | SCV003924725 | pathogenic | not provided | 2023-05-08 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect with impaired telomere replication, global genome instabilities, and decreased cell proliferation and survival (Gu et al., 2013; Chen et al., 2013, Wang et al., 2018); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23869908, 24115768, 22387016, 29481669, 33510405, 33780718) |
| OMIM | RCV000023993 | SCV000045284 | pathogenic | Cerebroretinal microangiopathy with calcifications and cysts 1 | 2012-03-09 | no assertion criteria provided | literature only |