Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000700684 | SCV000829450 | pathogenic | Autosomal recessive polycystic kidney disease | 2024-01-16 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 901 of the PKHD1 protein (p.Asn901Thr). This variant is present in population databases (rs764696718, gnomAD 0.01%). This missense change has been observed in individual(s) with polycystic kidney disease (PMID: 27225849, 30773290). 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: 577838). 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 80%. For these reasons, this variant has been classified as Pathogenic. |
Laboratory of Molecular Diagnosis of Genetic Disease, |
RCV001507099 | SCV001712070 | likely pathogenic | Caroli disease | 2021-05-05 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV001810482 | SCV002060098 | likely pathogenic | Polycystic kidney disease 4 | 2021-11-08 | criteria provided, single submitter | clinical testing | NM_138694.3(PKHD1):c.2702A>C(N901T) is a missense variant classified as likely pathogenic in the context of autosomal recessive polycystic kidney disease, PKHD1-related. N901T has been observed in cases with relevant disease (PMID: Raffaella_2017_(no PMID; thesis), 27225849, 30773290). Functional assessments of this variant are not available in the literature. N901T has been observed in population frequency databases (gnomAD: AMR 0.01%). In summary, NM_138694.3(PKHD1):c.2702A>C(N901T) is a missense variant that has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening. |
Gene |
RCV002469268 | SCV002765528 | likely pathogenic | not provided | 2022-12-16 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 30773290, 34426522, 27225849, 35715958) |
Baylor Genetics | RCV001810482 | SCV004204588 | likely pathogenic | Polycystic kidney disease 4 | 2023-08-09 | criteria provided, single submitter | clinical testing |