Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000545902 | SCV000629939 | likely pathogenic | Autosomal recessive polycystic kidney disease | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 326 of the PKHD1 protein (p.Gly326Val). This variant is present in population databases (rs778329699, gnomAD 0.0009%). This missense change has been observed in individual(s) with autosomal recessive polycystic kidney disease (PMID: 15805161; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 458610). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001731754 | SCV001983698 | uncertain significance | not specified | 2021-09-14 | criteria provided, single submitter | clinical testing | Variant summary: PKHD1 c.977G>T (p.Gly326Val) results in a non-conservative amino acid change located in the IPT domain (IPR002909) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. Several computational tools predict a significant impact on normal splicing: One predict the variant abolishes a 3` acceptor site. Three predict the variant weakens a 3` acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 251538 control chromosomes (gnomAD and publication data). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.977G>T has been reported in the literature in one individual affected with Polycystic Kidney And Hepatic Disease (Furu_2003). The data does not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Gene |
RCV001755812 | SCV001985394 | uncertain significance | not provided | 2022-08-04 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 12874454, 15805161) |
| Fulgent Genetics, |
RCV002483376 | SCV002799608 | uncertain significance | Polycystic kidney disease 4 | 2022-02-24 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV000545902 | SCV001463326 | uncertain significance | Autosomal recessive polycystic kidney disease | 2020-09-16 | no assertion criteria provided | clinical testing |