Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000685078 | SCV000812550 | likely pathogenic | Autosomal recessive polycystic kidney disease | 2023-12-18 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 35 of the PKHD1 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 PKHD1 are known to be pathogenic (PMID: 19940839). This variant is present in population databases (rs775638588, gnomAD 0.003%). Disruption of this splice site has been observed in individual(s) with clinical features of polycystic kidney disease (PMID: 29947050). ClinVar contains an entry for this variant (Variation ID: 565501). 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. |
| Fulgent Genetics, |
RCV002493135 | SCV002813916 | pathogenic | Polycystic kidney disease 4 | 2022-02-27 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV003332226 | SCV004040113 | pathogenic | not provided | 2023-03-26 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 29947050) |