Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000700536 | SCV000829295 | likely pathogenic | Autosomal recessive polycystic kidney disease | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 143 of the PKHD1 protein (p.Tyr143Cys). This variant is present in population databases (rs141093030, gnomAD 0.003%). This missense change has been observed in individual(s) with autosomal recessive polycystic kidney disease (PMID: 16523049, 27752906; 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: 577714). 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 not expected to disrupt PKHD1 protein function with a negative 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. |
Gene |
RCV001759393 | SCV001985432 | uncertain significance | not provided | 2020-01-10 | criteria provided, single submitter | clinical testing | Observed as heterozygous with no second variant identified in a patient with ARPKD in published literature (Gunay-Aygun et al., 2010); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 16523049, 19914852) |
Fulgent Genetics, |
RCV002485720 | SCV002801449 | uncertain significance | Polycystic kidney disease 4 | 2022-03-28 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000700536 | SCV002083408 | uncertain significance | Autosomal recessive polycystic kidney disease | 2020-12-01 | no assertion criteria provided | clinical testing |