Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000179136 | SCV000231335 | likely pathogenic | not provided | 2012-11-20 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001854440 | SCV002248966 | likely pathogenic | Autosomal recessive polycystic kidney disease | 2023-05-23 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 96433). This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. This variant is present in population databases (rs398124496, gnomAD 0.006%). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 2803 of the PKHD1 protein (p.Cys2803Tyr). 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. This variant disrupts the p.Cys2803 amino acid residue in PKHD1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19914852, 33532864). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |