ClinVar

Description

This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 29 of the AQP2 protein (p.Gly29Ser). This variant is present in population databases (no rsID available, gnomAD 0.01%). This missense change has been observed in individuals with autosomal recessive diabetes insipidus (PMID: 18473191, 23150186). 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 not expected to disrupt AQP2 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.