Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute for Clinical Genetics, |
RCV002540722 | SCV002009137 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002540722 | SCV003440528 | pathogenic | not provided | 2024-01-22 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 100 of the AQP2 protein (p.Gly100Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal recessive nephrogenic diabetes insipidus (PMID: 16845277). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1319413). 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 AQP2 protein function with a positive predictive value of 80%. This variant disrupts the p.Gly100 amino acid residue in AQP2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12050236). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |