Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
RCV002287704 | SCV002577846 | likely pathogenic | Polycystic kidney disease | 2021-09-29 | criteria provided, single submitter | clinical testing | ACMG categories: PM1,PM2,PP2,PP5 |
Invitae | RCV003502617 | SCV004292312 | likely pathogenic | Autosomal recessive polycystic kidney disease | 2023-08-25 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 1708331). This missense change has been observed in individual(s) with autosomal recessive polycystic kidney disease (PMID: 15698423). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 3178 of the PKHD1 protein (p.Gly3178Cys). |