Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000633432 | SCV000754656 | uncertain significance | Autosomal recessive polycystic kidney disease | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with proline at codon 8 of the PKHD1 protein (p.Leu8Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs750588859, ExAC 0.001%). This missense change has been observed in individual(s) with polycystic kidney disease (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Gene |
RCV001569911 | SCV001794080 | uncertain significance | not provided | 2021-05-24 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Prevention |
RCV003432661 | SCV004117702 | likely pathogenic | PKHD1-related condition | 2023-12-01 | criteria provided, single submitter | clinical testing | The PKHD1 c.23T>C variant is predicted to result in the amino acid substitution p.Leu8Pro. With a frameshifting variant, this variant has been reported in an individual with autosomal recessive polycystic kidney disease (ARPKD) (Burgmaier et al. 2021. PubMed ID: 33940108, Supplementary Table). In addition, at PreventionGenetics, we also found this variant in the compound heterozygous state with another frameshift variant in a patient tested for ARPKD. This variant is reported in 0.0026% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is interpreted as likely pathogenic. |
Natera, |
RCV000633432 | SCV001453293 | uncertain significance | Autosomal recessive polycystic kidney disease | 2020-09-16 | no assertion criteria provided | clinical testing |