Submissions for variant NM_144687.4(NLRP12):c.1738T>C (p.Cys580Arg)

dbSNP: rs1273259606

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000805940	SCV000945915	uncertain significance	Familial cold autoinflammatory syndrome 2	2018-12-23	criteria provided, single submitter	clinical testing	This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with arginine at codon 580 of the NLRP12 protein (p.Cys580Arg). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and arginine. This variant has not been reported in the literature in individuals with NLRP12-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.