Submissions for variant NM_001199138.2(NLRC4):c.617G>C (p.Ser206Thr)

gnomAD frequency: 0.00002  dbSNP: rs200612957

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001046241	SCV001210135	uncertain significance	Periodic fever-infantile enterocolitis-autoinflammatory syndrome; Familial cold autoinflammatory syndrome 4	2023-10-22	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 206 of the NLRC4 protein (p.Ser206Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NLRC4-related conditions. ClinVar contains an entry for this variant (Variation ID: 843582). 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 NLRC4 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002264155	SCV002542423	uncertain significance	Autoinflammatory syndrome	2016-12-12	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV001046241	SCV002780740	uncertain significance	Periodic fever-infantile enterocolitis-autoinflammatory syndrome; Familial cold autoinflammatory syndrome 4	2022-04-16	criteria provided, single submitter	clinical testing