Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000004328 | SCV000942874 | pathogenic | Autosomal recessive polycystic kidney disease | 2023-10-12 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg2671*) 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 (rs137852947, gnomAD 0.03%). This premature translational stop signal has been observed in individuals with PKHD1-related conditions (PMID: 11919560, 26695994, 27225849, 28364132). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 4112). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV000004328 | SCV001163030 | pathogenic | Autosomal recessive polycystic kidney disease | criteria provided, single submitter | clinical testing | ||
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000004328 | SCV001338100 | pathogenic | Autosomal recessive polycystic kidney disease | 2020-01-20 | criteria provided, single submitter | clinical testing | Variant summary: PKHD1 c.8011C>T (p.Arg2671X) 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 3.6e-05 in 251182 control chromosomes (gnomAD). c.8011C>T has been reported in the literature in multiple individuals affected with Polycystic Kidney and Hepatic Disease (e.g. Ward_2002, Obeidova_2015, Melchionda_2016). These data indicate that the variant is very 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 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Revvity Omics, |
RCV003137490 | SCV003822907 | pathogenic | Polycystic kidney disease 4 | 2022-03-17 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000004328 | SCV000024499 | pathogenic | Autosomal recessive polycystic kidney disease | 2002-03-01 | no assertion criteria provided | literature only | |
| Natera, |
RCV000004328 | SCV001459181 | pathogenic | Autosomal recessive polycystic kidney disease | 2020-09-16 | no assertion criteria provided | clinical testing |