Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| 3billion | RCV002250994 | SCV002521300 | pathogenic | Cone dystrophy 4 | 2022-05-22 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Canonical splice site: predicted to alter splicing and result in a loss or disruption of normal protein function. Multiple pathogenic loss-of-function variants are reported downstream of the variant. The variant is inherited from mother and shared with affected sibling (3billion dataset). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
| Labcorp Genetics |
RCV005095846 | SCV005777646 | likely pathogenic | not provided | 2024-05-23 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 19 of the PDE6C gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PDE6C are known to be pathogenic (PMID: 19887631, 23776498, 26103963, 30080950). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PDE6C-related conditions. ClinVar contains an entry for this variant (Variation ID: 1687312). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |