Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001243138 | SCV001416275 | uncertain significance | Autosomal recessive polycystic kidney disease | 2020-10-01 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Pro1791Leu amino acid residue in PKHD1. Other variant(s) that disrupt this residue have been observed in individuals with PKHD1-related conditions (PMID: 19940839), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with polycystic kidney disease (Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 968085). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with histidine at codon 1791 of the PKHD1 protein (p.Pro1791His). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and histidine. |