Submissions for variant NM_173842.3(IL1RN):c.272G>T (p.Cys91Phe)

gnomAD frequency: 0.00025  dbSNP: rs201638660

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000705510	SCV000834510	uncertain significance	Sterile multifocal osteomyelitis with periostitis and pustulosis	2022-11-01	criteria provided, single submitter	clinical testing	This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 94 of the IL1RN protein (p.Cys94Phe). This variant is present in population databases (rs201638660, gnomAD 0.04%). This missense change has been observed in individual(s) with chronic multifocal osteomyelitis (PMID: 22032624). ClinVar contains an entry for this variant (Variation ID: 581626). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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	RCV000997195	SCV001152391	uncertain significance	not provided	2018-11-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000705510	SCV001291963	uncertain significance	Sterile multifocal osteomyelitis with periostitis and pustulosis	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital	RCV000705510	SCV001984679	uncertain significance	Sterile multifocal osteomyelitis with periostitis and pustulosis	2019-12-23	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002263948	SCV002543454	uncertain significance	Autoinflammatory syndrome	2020-01-01	criteria provided, single submitter	clinical testing