Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000519595 | SCV000621449 | likely pathogenic | not provided | 2018-04-18 | criteria provided, single submitter | clinical testing | The E639X nonsense variant in the CEP290 gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). In summary, we consider this variant to be likely pathogenic. |
| Eurofins Ntd Llc |
RCV000519595 | SCV000702699 | pathogenic | not provided | 2016-11-18 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001058827 | SCV001223423 | pathogenic | Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis | 2022-05-20 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu639*) in the CEP290 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CEP290 are known to be pathogenic (PMID: 16909394, 17345604, 20690115). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CEP290-related conditions. ClinVar contains an entry for this variant (Variation ID: 452628). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV002497033 | SCV002811138 | likely pathogenic | Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 | 2021-09-01 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003155226 | SCV003844948 | likely pathogenic | Meckel syndrome, type 4 | 2023-02-17 | criteria provided, single submitter | clinical testing | Variant summary: CEP290 c.1915G>T (p.Glu639X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 150600 control chromosomes. To our knowledge, no occurrence of c.1915G>T in individuals affected with CEP290-related disorders and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submitters (evaluation after 2014) have cited the variant, and all laboratories classified the variant as pathogenic (n = 2) or likely pathogenic (n = 2). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV003470660 | SCV004216532 | likely pathogenic | Bardet-Biedl syndrome 14 | 2023-09-14 | criteria provided, single submitter | clinical testing |