Submissions for variant NM_173842.3(IL1RN):c.229G>T (p.Glu77Ter)

gnomAD frequency: 0.00001  dbSNP: rs121913161

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000015789	SCV000958698	pathogenic	Sterile multifocal osteomyelitis with periostitis and pustulosis	2023-10-13	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu80*) in the IL1RN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IL1RN are known to be pathogenic (PMID: 19494218, 21792839, 22940634, 26100510). This variant is present in population databases (rs121913161, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with interleukin 1 receptor antagonist deficiency (PMID: 19494218). This variant is also known as c.229G>T (E77X). ClinVar contains an entry for this variant (Variation ID: 14675). For these reasons, this variant has been classified as Pathogenic.
OMIM	RCV000015789	SCV000036056	pathogenic	Sterile multifocal osteomyelitis with periostitis and pustulosis	2009-06-04	no assertion criteria provided	literature only
Unité médicale des maladies autoinflammatoires, CHRU Montpellier	RCV000084165	SCV000116296	not provided	not provided		no assertion provided	not provided
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000084165	SCV001809064	pathogenic	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000084165	SCV001928370	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000084165	SCV001966824	pathogenic	not provided		no assertion criteria provided	clinical testing