Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV001004185 | SCV001163010 | likely pathogenic | Autosomal recessive polycystic kidney disease | criteria provided, single submitter | clinical testing | ||
| Invitae | RCV001004185 | SCV002234281 | pathogenic | Autosomal recessive polycystic kidney disease | 2023-11-21 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 3871 of the PKHD1 protein (p.Trp3871Arg). This variant is present in population databases (rs754626014, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of polycystic kidney disease (PMID: 15805161, 27491411, 32384486, 34536170). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 813370). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PKHD1 protein function. For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV002505537 | SCV002813858 | likely pathogenic | Polycystic kidney disease 4 | 2021-12-25 | criteria provided, single submitter | clinical testing | |
| 3billion | RCV002505537 | SCV003841286 | likely pathogenic | Polycystic kidney disease 4 | 2023-02-23 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.001%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.81; 3Cnet: 0.85). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000813370). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. |
| Baylor Genetics | RCV002505537 | SCV004204570 | likely pathogenic | Polycystic kidney disease 4 | 2023-08-23 | criteria provided, single submitter | clinical testing |