Submissions for variant NM_001370466.1(NOD2):c.1450A>G (p.Thr484Ala)

gnomAD frequency: 0.00005  dbSNP: rs759153904

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV002537131	SCV000940840	uncertain significance	Blau syndrome; Regional enteritis	2023-11-20	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 511 of the NOD2 protein (p.Thr511Ala). This variant is present in population databases (rs759153904, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with NOD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 646734). 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%. 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.
CeGaT Center for Human Genetics Tuebingen	RCV000996264	SCV001150912	uncertain significance	not provided	2018-05-01	criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000996264	SCV004026037	uncertain significance	not provided	2022-05-10	criteria provided, single submitter	clinical testing	PP3