Submissions for variant NM_012275.3(IL36RN):c.308G>A (p.Arg103Gln)

gnomAD frequency: 0.00009  dbSNP: rs542606182

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001944592	SCV002137119	uncertain significance	Generalized pustular psoriasis	2022-07-19	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 103 of the IL36RN protein (p.Arg103Gln). This variant is present in population databases (rs542606182, gnomAD 0.009%). This missense change has been observed in individual(s) with pustular skin disease (PMID: 28887889). ClinVar contains an entry for this variant (Variation ID: 1366264). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C35". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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	RCV002264409	SCV002543484	uncertain significance	Autoinflammatory syndrome	2019-09-01	criteria provided, single submitter	clinical testing