Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001377569 | SCV001574937 | pathogenic | Autosomal recessive polycystic kidney disease | 2021-04-20 | criteria provided, single submitter | clinical testing | This variant disrupts the initiator methionine in PKHD1. If translation initiates from the next in-frame methionine, the PKHD1 protein would no longer include the region containing the p.Leu8 amino acid residue. Other variant(s) that disrupt this residue have been observed in individuals with PKHD1-related conditions (Invitae), which suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. Disruption of the initiator codon has been observed in individual(s) with autosomal recessive polycystic kidney disease (PMID: 27225849). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (ExAC no frequency). This sequence change affects the initiator methionine of the PKHD1 mRNA. The next in-frame methionine is located at codon 9. |