Submissions for variant NM_003465.3(CHIT1):c.1155_1156+2del

dbSNP: rs143439055

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000360367	SCV000353406	uncertain significance	Chitotriosidase deficiency	2017-04-27	criteria provided, single submitter	clinical testing	The CHIT1 c.1155_1156+2delGAGT variant occurs in a canonical splice site (donor) and is therefore predicted to disrupt or distort the normal gene product. The variant has been reported in one study where CHIT1 genotyping of patients with Gaucher disease was performed to assess possible issues with therapeutic monitoring (Adelino et al. 2012). In this study, the c.1155_1156+2delGAGT variant was found in a one patient with Gaucher disease along with a second missense variant that is known to reduce chitotriosidase enzyme activity. It was noted that this patient also carried a common allele in this gene (duplication of 24 bp in exon 11 of the CHIT1 gene): an allele which is known to lead to an absence of chitotriosidase enzyme activity. The phase of these variants in this individual is unknown. Control data are unavailable for this variant, which is reported at a frequency of 0.12963 in the Yoruba Nigerian population of the 1000 Genomes Project. Based on the potential impact of splice variants and the limited evidence, the c.1155_1156+2delGAGT variant is classified as a variant of unknown significance but suspicious for pathogenicity for chitotriosidase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae	RCV000360367	SCV000651333	benign	Chitotriosidase deficiency	2024-01-29	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000675719	SCV000801433	uncertain significance	not provided	2015-12-16	no assertion criteria provided	clinical testing