Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000633422 | SCV000754644 | likely pathogenic | Autosomal recessive polycystic kidney disease | 2023-12-09 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 2477 of the PKHD1 protein (p.Phe2477Cys). This variant is present in population databases (no rsID available, gnomAD 0.002%). This missense change has been observed in individual(s) with polycystic kidney disease (PMID: 33940108). 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: 528290). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PKHD1 protein function with a positive predictive value of 95%. 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. |
Eurofins Ntd Llc |
RCV000731567 | SCV000859405 | uncertain significance | not provided | 2018-01-26 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002477389 | SCV002801311 | uncertain significance | Polycystic kidney disease 4 | 2022-02-23 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000731567 | SCV003852839 | uncertain significance | not provided | 2022-09-28 | criteria provided, single submitter | clinical testing | Not observed at 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: 33940108) |
Natera, |
RCV000633422 | SCV002078025 | uncertain significance | Autosomal recessive polycystic kidney disease | 2018-09-14 | no assertion criteria provided | clinical testing |