Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory of Molecular Genetics, |
RCV001257511 | SCV001434244 | likely pathogenic | Autosomal recessive polycystic kidney disease | 2020-09-30 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003235520 | SCV003934195 | uncertain significance | not specified | 2023-05-18 | criteria provided, single submitter | clinical testing | Variant summary: PKHD1 c.2170C>T (p.Pro724Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250710 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2170C>T has been reported in the literature as a compound heterozygous genotype in at-least one individual affected with features of Polycystic Kidney And Hepatic Disease (example, Burgmaier_2021 captured in Wicher_2020). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 15698423, 33940108, 33282801). 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 likely pathogenic. Based on the evidence outlined above, the variant was classified as uncertain significance. |