Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781730 | SCV000920001 | pathogenic | Autosomal recessive polycystic kidney disease | 2021-07-05 | criteria provided, single submitter | clinical testing | Variant summary: PKHD1 c.10955delC (p.Pro3652GlnfsX2) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 250876 control chromosomes. c.10955delC has been reported in the literature in individuals affected with Polycystic Kidney And Hepatic Disease (e.g. Gunay-Aygun_2009, Tong_2016). 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. One other clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and cited the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Invitae | RCV000781730 | SCV001587249 | pathogenic | Autosomal recessive polycystic kidney disease | 2023-09-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Pro3652Glnfs*2) 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). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 633361). This premature translational stop signal has been observed in individual(s) with autosomal recessive polycystic kidney disease (PMID: 19914852). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. |
| Baylor Genetics | RCV003467315 | SCV004204784 | pathogenic | Polycystic kidney disease 4 | 2022-07-03 | criteria provided, single submitter | clinical testing |