NM_000214.3(JAG1):c.558_567del (p.Cys187fs) AND Alagille syndrome due to a JAG1 point mutation

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 4, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001054177.5

Allele description [Variation Report for NM_000214.3(JAG1):c.558_567del (p.Cys187fs)]

NM_000214.3(JAG1):c.558_567del (p.Cys187fs)

Gene:

JAG1:jagged canonical Notch ligand 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

20p12.2

Genomic location:

Preferred name:

NM_000214.3(JAG1):c.558_567del (p.Cys187fs)

HGVS:

NC_000020.11:g.10658599_10658608del
NG_007496.1:g.20443_20452del
NM_000214.3:c.558_567delMANE SELECT
NP_000205.1:p.Cys187fs
LRG_1191t1:c.558_567del
LRG_1191:g.20443_20452del
LRG_1191p1:p.Cys187fs
NC_000020.10:g.10639243_10639252del
NC_000020.10:g.10639247_10639256del
NM_000214.2:c.558_567del

Protein change:

C187fs

Links:

dbSNP: rs2067393679

NCBI 1000 Genomes Browser:

rs2067393679

Molecular consequence:

NM_000214.3:c.558_567del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Alagille syndrome due to a JAG1 point mutation
Synonyms:: HEPATIC DUCTULAR HYPOPLASIA, SYNDROMATIC; Alagille syndrome 1; JAG1-Related Alagille Syndrome
Identifiers:: MONDO: MONDO:0016862; MedGen: C1956125; Orphanet: 52; OMIM: 118450

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001218480	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 4, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 11180599, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001218480

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 4, 2019)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutation analysis of Jagged1 (JAG1) in Alagille syndrome patients.

Colliton RP, Bason L, Lu FM, Piccoli DA, Krantz ID, Spinner NB.

Hum Mutat. 2001 Feb;17(2):151-2.

PubMed [citation]

PMID:: 11180599

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001218480.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in JAG1 are known to be pathogenic (PMID: 11180599). This variant has not been reported in the literature in individuals with JAG1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Cys187Thrfs*222) in the JAG1 gene. It is expected to result in an absent or disrupted protein product.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 30, 2024

ClinVar

Relating variation to medicine