Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000670400 | SCV000795247 | uncertain significance | Autosomal recessive polycystic kidney disease | 2017-11-01 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000670400 | SCV002274070 | likely pathogenic | Autosomal recessive polycystic kidney disease | 2023-06-04 | 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: 554720). This missense change has been observed in individual(s) with PKHD1-related conditions (PMID: 26385851). 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. This variant is present in population databases (no rsID available, gnomAD 0.004%). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 311 of the PKHD1 protein (p.Thr311Ala). |