Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000627200 | SCV000748185 | pathogenic | not provided | 2018-04-24 | criteria provided, single submitter | clinical testing | The R477X nonsense variant in the CEP290 gene has been reported previously in an individual with Leber congenital amaurosis who had a second CEP290 variant identified (Wiszniewski et al., 2011). The R477X variant was also observed in apparent homozygous state in a patient with Meckel-Gruber syndrome (Szymanska et al., 2012). The R477X variant is not observed in large population cohorts (Lek et al., 2016). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. |
| Fulgent Genetics, |
RCV000763316 | SCV000893993 | pathogenic | Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 | 2021-12-10 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000779118 | SCV000915612 | likely pathogenic | CEP290-Related Disorders | 2018-12-04 | criteria provided, single submitter | clinical testing | The CEP290 c.1429C>T (p.Arg477Ter) variant is a stop-gained variant that is predicted to result in a premature termination of the protein. The p.Arg477Ter variant has been reported in at least three studies in which it is found in three individuals including one individual with Meckel syndrome in whom the variant was present in a homozygous state and two individuals with Leber congenital amaurosis in whom the variant was present in a compound heterozygous state with a splice variant on the second allele (Wiszniewski et al. 2011; Szymanska et al. 2012; Wang et al. 2015). The p.Arg477Ter variant was absent from 192 controls (Wiszniewski et al. 2011; Szymanska et al. 2012), and is not found in the 1000 Genomes Project, the Exome Sequencing Project, the Exome Aggregation Consortium, or the Genome Aggregation Database. Based on the evidence, the p.Arg477Ter variant is classified as likely pathogenic for CEP290-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Invitae | RCV000814304 | SCV000954707 | pathogenic | Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis | 2023-07-19 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 523768). This premature translational stop signal has been observed in individuals with CEP290-related conditions (PMID: 21153841, 23351400, 26047050). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Arg477*) 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). |
| Baylor Genetics | RCV003465363 | SCV004216614 | pathogenic | Bardet-Biedl syndrome 14 | 2023-06-17 | criteria provided, single submitter | clinical testing |