Submissions for variant NM_012275.3(IL36RN):c.277A>G (p.Lys93Glu)

gnomAD frequency: 0.00001  dbSNP: rs746109701

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002264632	SCV002543480	uncertain significance	Autoinflammatory syndrome	2021-02-26	criteria provided, single submitter	clinical testing
Invitae	RCV003095934	SCV003493519	uncertain significance	Generalized pustular psoriasis	2022-04-17	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 93 of the IL36RN protein (p.Lys93Glu). This variant is present in population databases (rs746109701, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with IL36RN-related conditions. 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 glutamic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.