Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000670639 | SCV000795517 | uncertain significance | Autosomal recessive polycystic kidney disease | 2017-11-08 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002469249 | SCV002766524 | uncertain significance | not specified | 2022-11-03 | criteria provided, single submitter | clinical testing | Variant summary: PKHD1 c.11869C>T (p.Arg3957Cys) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 7.2e-05 in 250414 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in PKHD1 causing Polycystic Kidney And Hepatic Disease (7.2e-05 vs 0.0071), allowing no conclusion about variant significance. c.11869C>T has been reported in the literature in an individuals affected with Polycystic Kidney And Hepatic Disease who carried two pathogenic variants that explain the disease in this patient, and was shown to be in cis with one of the variants (Gunay-Aygun_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. One laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |