Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000615076 | SCV000711721 | pathogenic | Renal dysplasia and retinal aplasia | 2017-09-01 | criteria provided, single submitter | clinical testing | The p.Arg455X variant in IQCB1 (previously named NPHP5) has been reported in 1 h omozygous individual with Senior-L?ken syndrome (Chaki 2011), and in 1 child wit h Leber congenital amaurosis (LCA), in trans with another pathogenic IQCB1 varia nt (Stone 2011). This variant was absent from large population studies. This non sense variant leads to a premature termination codon at position 455 which is pr edicted to lead to a truncated or absent protein. Nonsense and other variants le ading to loss of function of the IQCB1 protein are an established cause of Senio r-L?ken syndrome. In summary, this variant meets our criteria to be classified a s pathogenic for Seni?r-Loken syndrome in an autosomal recessive manner based up on its presence in affected individuals, absence from controls, and predicted im pact on the protein. |
| Labcorp Genetics |
RCV002529304 | SCV003525347 | pathogenic | Nephronophthisis | 2022-02-13 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 504877). This premature translational stop signal has been observed in individual(s) with Leber congenital amaurosis and Senior-L√∏ken syndrome (PMID: 21220633, 21866095). This sequence change creates a premature translational stop signal (p.Arg455*) in the IQCB1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IQCB1 are known to be pathogenic (PMID: 15723066, 21901789, 23559409, 28041643). |
| Baylor Genetics | RCV004568321 | SCV005059756 | pathogenic | Senior-Loken syndrome 5 | 2024-03-19 | criteria provided, single submitter | clinical testing | |
| Institute of Human Genetics, |
RCV004817814 | SCV005070700 | pathogenic | Retinal dystrophy | 2020-01-01 | criteria provided, single submitter | clinical testing | |
| 3billion | RCV004568321 | SCV005905801 | pathogenic | Senior-Loken syndrome 5 | 2023-10-30 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Predicted Consequence/Location: Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic without evidence for the classification (ClinVar ID: VCV000504877 /PMID: 21220633). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. |