Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002528895 | SCV000759525 | uncertain significance | Blau syndrome; Regional enteritis | 2023-07-28 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 426 of the NOD2 protein (p.Arg426His). This variant is present in population databases (rs562225614, gnomAD 0.02%). This missense change has been observed in individual(s) with early-onset inflammatory bowel disease (PMID: 29697845). ClinVar contains an entry for this variant (Variation ID: 531600). Experimental studies have shown that this missense change affects NOD2 function (PMID: 29697845). 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 NOD2 protein function. 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. |