Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001953441 | SCV002241266 | pathogenic | Autosomal recessive polycystic kidney disease | 2021-08-26 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with glycine at codon 3154 of the PKHD1 protein (p.Asp3154Gly). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with polycystic kidney disease (PMID: 19940839; Invitae). 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. For these reasons, this variant has been classified as Pathogenic. |
Prevention |
RCV003893017 | SCV004708998 | likely pathogenic | PKHD1-related disorder | 2024-03-01 | criteria provided, single submitter | clinical testing | The PKHD1 c.9461A>G variant is predicted to result in the amino acid substitution p.Asp3154Gly. This variant has been reported with a pathogenic PKHD1 missense variant (c.5912G>A, p.Gly1971Asp) in an individual with autosomal recessive polycystic kidney disease (ARPKD) (Table S2 of Denamur et al. 2010. PubMed ID: 19940839). In addition, we have also found this variant with a different pathogenic PKHD1 missense variant (c.2864T>G, p.Phe955Cys) in an infant with polycystic kidney disease at PreventionGenetics. In ClinVar, another lab reported they found this variant in individuals with polycystic kidney disease and classify it as pathogenic (https://preview.ncbi.nlm.nih.gov/clinvar/variation/1456801/). This variant has not been reported in a large population database, indicating this variant is rare. Given this evidence, this variant is interpreted as likely pathogenic. |