Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000169522 | SCV000220996 | likely pathogenic | Autosomal recessive polycystic kidney disease | 2014-12-29 | criteria provided, single submitter | literature only | |
| Centre for Mendelian Genomics, |
RCV000415273 | SCV000493006 | pathogenic | Polycystic kidney disease; Renal cyst; Ventricular hypertrophy | 2014-08-21 | criteria provided, single submitter | clinical testing | |
| Centre for Mendelian Genomics, |
RCV000626994 | SCV000747697 | pathogenic | Polycystic kidney disease | 2017-01-01 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000169522 | SCV002230765 | pathogenic | Autosomal recessive polycystic kidney disease | 2021-12-02 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 189110). This premature translational stop signal has been observed in individual(s) with polycystic kidney disease (PMID: 12874454). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp937*) 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). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000169522 | SCV002571792 | likely pathogenic | Autosomal recessive polycystic kidney disease | 2022-08-05 | criteria provided, single submitter | clinical testing | Variant summary: PKHD1 c.2810G>A (p.Trp937X) 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 was absent in 251102 control chromosomes (gnomAD). c.2810G>A has been reported in the literature in individuals affected with Polycystic Kidney And Hepatic Disease, with at least two confirmed biallelic genotypes (e.g. Furu_2003, Obeidova_2015). 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. Two ClinVar submitters have assessed the variant since 2014: both classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |