Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Molecular Genetics Laboratory, |
RCV001199701 | SCV001162541 | pathogenic | Retinitis pigmentosa | 2020-01-09 | criteria provided, single submitter | research | |
| Labcorp Genetics |
RCV001860548 | SCV002242632 | pathogenic | not provided | 2023-09-21 | 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: 813188). This variant has not been reported in the literature in individuals affected with LCA5-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Lys172Asnfs*3) in the LCA5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LCA5 are known to be pathogenic (PMID: 17546029, 23946133). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002282423 | SCV002572095 | likely pathogenic | Leber congenital amaurosis | 2022-08-16 | criteria provided, single submitter | clinical testing | Variant summary: LCA5 c.516_519delAGAA (p.Lys172AsnfsX3) 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 withing ClinVar (e.g. c.763C>T [p.Arg255Ter], c.838C>T [p.Arg280Ter]). The variant allele was found at a frequency of 4e-06 in 250850 control chromosomes (gnomAD). c.516_519delAGAA has been reported in the literature in at least one compound heterozygous individual affected with sporadic retinitis pigmentosa (e.g. Weisschuh_2020), however this individual did not have a diagnosis of Leber Congenital Amaurosis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and both classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV003473543 | SCV004190595 | likely pathogenic | Leber congenital amaurosis 5 | 2023-10-17 | criteria provided, single submitter | clinical testing |