Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000669544 | SCV000794305 | uncertain significance | Autosomal recessive polycystic kidney disease | 2017-10-06 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000669544 | SCV004292310 | pathogenic | Autosomal recessive polycystic kidney disease | 2024-01-30 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 3740 of the PKHD1 protein (p.Pro3740Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with polycystic kidney disease (PMID: 15698423). 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. ClinVar contains an entry for this variant (Variation ID: 553997). 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) performed at Invitae indicates that this missense variant is expected to disrupt PKHD1 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004702289 | SCV005204714 | uncertain significance | not specified | 2024-06-18 | criteria provided, single submitter | clinical testing | Variant summary: PKHD1 c.11218C>T (p.Pro3740Ser) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251182 control chromosomes (gnomAD). c.11218C>T has been reported in the literature in two siblings from a family affected with autosomal recessive polycystic kidney disease where it was seen in trans with a pathogenic variant (Bergmann_2005). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 15698423). ClinVar contains an entry for this variant (Variation ID: 553997). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |