Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003764528 | SCV004571000 | pathogenic | Blau syndrome; Regional enteritis | 2023-12-28 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 382 of the NOD2 protein (p.Asp382Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of Blau syndrome (PMID: 15459013, 21596301, 24713464). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 4699). 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 with a positive predictive value of 80%. Experimental studies have shown that this missense change affects NOD2 function (PMID: 15459013). For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000416482 | SCV000025140 | pathogenic | Blau syndrome | 2005-02-01 | no assertion criteria provided | literature only | |
Unité médicale des maladies autoinflammatoires, |
RCV000416482 | SCV000116204 | not provided | Blau syndrome | no assertion provided | not provided |