Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Broad Center for Mendelian Genomics, |
RCV000785965 | SCV000924548 | likely pathogenic | Joubert syndrome 5 | 2018-06-15 | criteria provided, single submitter | research | The homozygous p.Lys1598SerfsTer8 variant was identified by our study in an individual with Joubert syndrome. This variant was absent from large population studies. Loss of function of the CEP290 gene is an established disease mechanism in autosomal recessive Joubert syndrome, and this is a loss of function variant. In summary, although additional studies are required to fully establish its pathogenicity, this variant is likely pathogenic. |
| Fulgent Genetics, |
RCV002477791 | SCV002789599 | pathogenic | Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 | 2021-08-23 | criteria provided, single submitter | clinical testing | |
| Broad Center for Mendelian Genomics, |
RCV002535732 | SCV003761325 | pathogenic | CEP290-related ciliopathy | 2023-01-25 | criteria provided, single submitter | curation | The homozygous p.Lys1598SerfsTer8 variant in CEP290 was identified by our study in one individual with Joubert syndrome. The p.Lys1598SerfsTer8 variant in CEP290 has been previously reported in one individual with Joubert syndrome 5 (PMID: 17564967). This affected individual (PMID: 17564967) and the individual identified by our study were homozygotes, which increases the likelihood that the p.Lys1598SerfsTer8 variant in CEP290 is pathogenic. This variant has also been reported in ClinVar (Variation ID: 635087) and has been interpreted as likely pathogenic by the Broad Rare Disease Group. This variant was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1598 and leads to a premature termination codon 8 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the CEP290 gene is an established disease mechanism of autosomal recessive Joubert syndrome 5. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Joubert syndrome 5. ACMG/AMP Criteria applied: PVS1, PM2_Supporting, PM3 (Richards 2015). |
| Al Jalila Children’s Genomics Center, |
RCV004798871 | SCV005420392 | pathogenic | Leber congenital amaurosis 10 | 2024-10-04 | criteria provided, single submitter | research | PVS1,PM2,PM3 |