VCV000009524.1 - ClinVar

NM_003465.3(CHIT1):c.[1060G>A;1155G>A1156+6_1156+9del]

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Affects

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

This haplotype includes the following variants

NM_003465.3(CHIT1):c.[1060G>A;1155G>A1156+6_1156+9del]

Other names: CHIT1, GLY354ARG, LEU385LEU, AND 4-BP DEL
Functional consequence: -
Links: OMIM: 600031.0002

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
CHIT1		-	-	GRCh38 GRCh37	192	209

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Chitotriosidase deficiency	Affects (1)	no assertion criteria provided	Sep 1, 2007	RCV000010132.12

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Affects (Sep 01, 2007)	no assertion criteria provided Method: literature only	CHITOTRIOSIDASE DEFICIENCY Affected status: not provided Allele origin: germline	OMIM Accession: SCV000030353.2 First in ClinVar: Apr 04, 2013 Last updated: Jan 06, 2017	Publications: PubMed (1) PubMed: 17464953 Comment on evidence: In a Caribbean Hispanic/African type 1 Gaucher disease (230800) patient with chitotriosidase deficiency (CHITD; 614122), Grace et al. (2007) identified a complex allele of the … (more) In a Caribbean Hispanic/African type 1 Gaucher disease (230800) patient with chitotriosidase deficiency (CHITD; 614122), Grace et al. (2007) identified a complex allele of the CHIT1 gene with 3 different variations in cis: a 1060G-A transition in exon 10 resulting in a gly354-to-arg (G354R) substitution, a 1155G-A transition in exon 10 resulting in a synonymous leu385-to-leu (L385L) substitution, and a 4-bp deletion in intron 10 (1156delGTAA). The complex allele was designated 'E/I-10' (exon/intron-10) allele. The patient was compound heterozygous for the E/I-10 complex allele and the common 24-bp duplication (600031.0001). In vitro functional expression studies showed that the complex mutant had no residual enzyme activity. Further screening identified the complex allele in individuals of Caribbean Hispanic, Dominican, Caribbean Black, Puerto Rican, and American Black descent. It was not identified in those of Caucasian or Ashkenazi Jewish descent. (less)

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Chitotriosidase deficiency: a mutation update in an african population.	Arndt S	JIMD reports	2013	PMID: 23430794
Biochemical and Molecular Chitotriosidase Profiles in Patients with Gaucher Disease Type 1 in Minas Gerais, Brazil: New Mutation in CHIT1 Gene.	Adelino TER	JIMD reports	2013	PMID: 23430552
Human chitotriosidase polymorphisms G354R and A442V associated with reduced enzyme activity.	Lee P	Blood cells, molecules & diseases	2007	PMID: 17693102
Type 1 Gaucher disease: null and hypomorphic novel chitotriosidase mutations-implications for diagnosis and therapeutic monitoring.	Grace ME	Human mutation	2007	PMID: 17464953
Type 1 Gaucher disease: null and hypomorphic novel chitotriosidase mutations-implications for diagnosis and therapeutic monitoring.	Grace ME	Human mutation	2007	PMID: 17464953

Text-mined citations for this variant ...

Record last updated Nov 10, 2024

ClinVar Genomic variation as it relates to human health

NM_003465.3(CHIT1):c.[1060G>A;1155G>A1156+6_1156+9del]

Variant Details

NM_003465.3(CHIT1):c.[1060G>A;1155G>A1156+6_1156+9del]

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...