Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000667214 | SCV000791632 | uncertain significance | Autosomal recessive polycystic kidney disease | 2017-05-19 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000667214 | SCV002571027 | likely pathogenic | Autosomal recessive polycystic kidney disease | 2022-07-30 | criteria provided, single submitter | clinical testing | Variant summary: PKHD1 c.8552T>C (p.Ile2851Thr) results in a non-conservative amino acid change located in the G8 domain (IPR019316) of 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 248318 control chromosomes. c.8552T>C has been reported in the literature as a homozygous and compound heterozygous genotype in individuals affected with Autosomal recessive polycystic kidney disease (example, Bergmann_2005, Szabo_2018, Burgmaier_2021). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Invitae | RCV000667214 | SCV004292313 | pathogenic | Autosomal recessive polycystic kidney disease | 2023-09-09 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2851 of the PKHD1 protein (p.Ile2851Thr). For these reasons, this variant has been classified as Pathogenic. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 552021). This missense change has been observed in individual(s) with autosomal recessive polycystic kidney disease (PMID: 15698423, 29956005, 33940108). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). |
| Zotz- |
RCV003387905 | SCV004099399 | likely pathogenic | Polycystic kidney disease 4 | 2023-10-30 | no assertion criteria provided | clinical testing |