Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000474720 | SCV000545845 | pathogenic | Autosomal recessive polycystic kidney disease | 2023-08-22 | criteria provided, single submitter | clinical testing | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PKHD1 protein function. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 406889). This missense change has been observed in individual(s) with autosomal recessive polycystic kidney disease (PMID: 15108281, 15698423; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs751084512, gnomAD 0.2%). This sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 2303 of the PKHD1 protein (p.Ile2303Phe). |
| Fulgent Genetics, |
RCV002481410 | SCV002785372 | likely pathogenic | Polycystic kidney disease 4 | 2022-02-28 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV002481410 | SCV004204729 | pathogenic | Polycystic kidney disease 4 | 2023-02-09 | criteria provided, single submitter | clinical testing |