Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003079067 | SCV003459963 | pathogenic | Autosomal recessive polycystic kidney disease | 2023-01-24 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 2665 of the PKHD1 protein (p.Leu2665Pro). For these reasons, this variant has been classified as Pathogenic. 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. This missense change has been observed in individual(s) with clinical features of polycystic kidney disease (PMID: 28851938, 30507656, 31328266, 34487536). 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 not present in population databases (gnomAD no frequency). |
| Baylor Genetics | RCV003459737 | SCV004204560 | pathogenic | Polycystic kidney disease 4 | 2023-08-31 | criteria provided, single submitter | clinical testing |