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Alagille Syndrome-1 via the JAG1 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
JAG1 81407 81407,81406 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
15253JAG181407 81407,81406 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Chansonette Badduke, PhD

Clinical Features and Genetics

Clinical Features

Alagille syndrome (ALGS1) is characterized clinically by cholestasis, congenital heart defects, ophthalmic findings, vertebral defects, and characteristic facies. Abnormally low numbers of hepatic bile ducts results in chronic cholestasis, which can lead to cirrhosis and end-stage liver disease. However, hepatic manifestations are variable, and some patients present with jaundice but do not progress to more serious disease. Right-sided cardiac defects are found in almost all patients with pulmonic stenosis being the most common single finding (67%; Emerick et al. 1999). Posterior embryotoxon is the most common ophthalmic finding, affecting approximately 80% of all individuals with Alagille syndrome (Emerick et al. 1999). Butterfly vertebrae, the most frequent skeletal anomaly, have been found in nearly 90% of patients (Sanderson et al. 2002). Other skeletal findings include hemivertebrae and rib anomalies. Typical facial features of Alagille syndrome include deep-set eyes with moderate hypertelorism, a broad forehead, a prominent pointed chin, and a long straight nose with a bulbous tip. Vascular anomalies and intracranial bleeding are recognized as a significance risk for morbidity and mortality in Alagille syndrome (Lykavieris et al. 2004; Kamath et al. 2004).


Alagille syndrome is inherited as an autosomal dominant disorder with reduced penetrance. Approximately 30% to 50% of Alagille syndrome patients have an affected parent and approximately 50% to 70% have de novo JAG1 variants. Somatic mosaicism for JAG1 variants has been reported in five of sixty-one cases (Giannakudis et al. 2001). Haploinsufficiency for JAG1 results from intragenic variants (~90%) or a 20p12 microdeletion (~7%) encompassing all of JAG1 (Warthen et al. 2006; Spinner, Krantz and Kamath 2010). One study of 53 variant-positive relatives of probands found that 96% had some feature of the condition (Kamath et al. 2003), although a significant number of individuals (47%) had features that were subclinical. Over 300 JAG1 variants have been described. Missense and nonsense are the most abundant class of variant and are distributed throughout the gene.

Clinical Sensitivity - Sequencing with CNV PG-Select

Clinical sensitivity of the JAG1 sequencing test has been shown to be high in patients meeting rigorous phenotypic criteria for this disorder. Warthen et al. (2006) identified intragenic JAG1 point variants in almost 90% of a cohort of 247 Alagille syndrome patients. Much less common etiologies include a 20p12 microdeletion detectable by FISH (<10%; Spinner, Krantz and Kamath, 2010) and NOTCH2 gene variants detectable by sequence analysis (<1%; McDaniell et al. 2006). Limited sensitivity for detecting JAG1 variants among individuals not meeting rigorous phenotypic criteria may be a consequence of a significant rate of mosaicism (Giannakudis et al. 2001).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This test provides full coverage of all coding exons of the JAG1 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Individuals with liver, cardiac, skeletal, ophthalmic, and facial findings consistent with Alagille syndrome. Because clinical manifestations exhibit inter- and intrafamilial variability, not all variant-proven cases will have a classic presentation.


Official Gene Symbol OMIM ID
JAG1 601920
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Alagille Syndrome 1 AD 118450


  • Emerick KM, Rand EB, Goldmuntz E, Krantz ID, Spinner NB, Piccoli DA. 1999. Features of Alagille syndrome in 92 patients: frequency and relation to prognosis. Hepatology 29: 822–829. PubMed ID: 10051485
  • Giannakudis J, Ropke A, Kujat A, Krajewska-Walasek M, Hughes H, Fryns J-P, Bankier A, Amor D, Schlicker M, Hansmann I. 2001. Parental mosaicism of JAG1 mutations in families with Alagille syndrome. European Journal of Human Genetics 9: 209–216. PubMed ID: 11313761
  • Kamath BM, Bason L, Piccoli DA, Krantz ID, Spinner NB. 2003. Consequences of JAG1 mutations. Journal of medical genetics 40: 891–895. PubMed ID: 14684686
  • Kamath BM, Spinner NB, Emerick KM, Chudley AE, Booth C, Piccoli DA, Krantz ID. 2004. Vascular Anomalies in Alagille Syndrome: A Significant Cause of Morbidity and Mortality. Circulation 109: 1354–1358. PubMed ID: 14993126
  • Lykavieris P, Crosnier C, Trichet C, Meunier-Rotival M, Hadchouel M. 2003. Bleeding Tendency in Children With Alagille Syndrome. Pediatrics 111: 167–170. PubMed ID: 12509572
  • McDaniell R, Warthen DM, Sanchez-Lara PA, Pai A, Krantz ID, Piccoli DA, Spinner NB. 2006. NOTCH2 Mutations Cause Alagille Syndrome, a Heterogeneous Disorder of the Notch Signaling Pathway. The American Journal of Human Genetics 79: 169–173. PubMed ID: 16773578
  • Sanderson, Vanessa Newman, Susan F. E. 2002. Vertebral anomalies in children with Alagille syndrome: an analysis of 50 consecutive patients. Pediatric Radiology 32: 114–119. PubMed ID: 11819079
  • Spinner NB, Leonard LD, Krantz ID. 2010. Alagille Syndrome. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301450
  • Warthen DM, Moore EC, Kamath BM, Morrissette JJD, Sanchez-Lara PA, Sanchez P, Piccoli DA, Krantz ID, Spinner NB. 2006. Jagged1 (JAG1) mutations in Alagille syndrome: increasing the mutation detection rate. Hum. Mutat. 27: 436–443. PubMed ID: 16575836


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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