Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000169068 | SCV000220233 | likely pathogenic | Autosomal recessive polycystic kidney disease | 2014-04-08 | criteria provided, single submitter | literature only | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000169068 | SCV000918015 | pathogenic | Autosomal recessive polycystic kidney disease | 2022-05-06 | criteria provided, single submitter | clinical testing | Variant summary: PKHD1 c.11524C>T (p.Arg3842X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 1.6e-05 in 250860 control chromosomes. c.11524C>T has been reported in the literature in compound heterozygosity in at-least one individual affected with Autosomal Recessive Polycystic Kidney And Hepatic Disease and also subsequently cited by others (example, Sharp_2005, Denamur_2010). 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 pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Invitae | RCV000169068 | SCV002235839 | pathogenic | Autosomal recessive polycystic kidney disease | 2022-07-20 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg3842*) in the PKHD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PKHD1 are known to be pathogenic (PMID: 19940839). This variant is present in population databases (rs746471701, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with clinical features of polycystic kidney disease (PMID: 15805161). ClinVar contains an entry for this variant (Variation ID: 188754). For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV003462264 | SCV004204617 | pathogenic | Polycystic kidney disease 4 | 2023-07-02 | criteria provided, single submitter | clinical testing |