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Maturity Onset Diabetes of the Young (MODY) via the APPL1 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
9831 APPL1 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9831APPL181479 81479,81479 $990 Order Options and Pricing

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

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Fang Xu, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Maturity onset diabetes of the young (MODY), a primary pancreatic beta-cell defect, is the most common type of monogenic diabetes, accounting for up to 5% of young adults diagnosed with diabetes (Owen. 2013. PubMed ID: 23760703; McDonald and Ellard. 2013. PubMed ID: 23878349). MODY typically presents in lean young adults before 25 years with an autosomal dominant family history. MODY patients have continued production of endogenous insulin, absence of beta-cell autoimmunity and absence of signs of insulin resistance. As this non-insulin dependent type of diabetes is frequently misdiagnosed as Type 1 or Type 2 diabetes, a timely and accurate molecular diagnosis of MODY is essential to treatment decisions, prognosis, family screening and obstetric management of gestational diabetes (Ellard et al. 2008. PubMed ID: 18297260). MODY has been conventionally classified into 14 types in terms of causative genes. The APPL1 gene was reported to cause familial diabetes mellitus due to heterozygous loss-of-function variants (Prudente. 2015. PubMed ID: 26073777).

Genetics

MODY is inherited in an autosomal dominant manner. Proteins encoded by MODY-associated genes include nuclear transcription factors controlling pancreatic development (HNF1A, HNF4A, HNF1B, PDX1, KLF11, PAX4 and NEUROD1), glucokinase (a glucose sensor in pancreatic beta-cells) (GCK), insulin (INS), kinase stimulating insulin synthesis and secretion (BLK), the enzyme carboxyl ester lipase (CEL), the ATP-sensitive potassium (KATP) channels (ABCC8 and KCNJ11) and glucose metabolism (APPL1).

The APPL1 gene (22 coding exons) encodes the Adaptor Protein, Phosphotyrosine Interaction, PH domain, and leucine zipper containing 1, which plays a key regulatory role in glucose metabolism. To date, only two loss-of-function variants (a missense and a nonsense variant) in APPL1 have been reported to cause familial diabetes mellitus (Prudente. 2015. PubMed ID: 26073777). Large deletions and duplications have not been reported (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

In a whole-exome sequencing study of 60 families with familial diabetes mellitus but without pathogenic variants found in the six most common MODY genes (HNF4A, GCK, HNF1A, PDX1, HNF1B and NEUROD1), heterozygous pathogenic variants in APPL1 were detected in two families (3.3%) (Prudente. 2015. PubMed ID: 26073777).

Testing Strategy

This test provides full coverage of all coding exons of the APPL1 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. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Candidates for this test are patients with MODY.

Gene

Official Gene Symbol OMIM ID
APPL1 604299
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Maturity-Onset Diabetes Of The Young, Type 14 AD 616511

Related Test

Name
Maturity Onset Diabetes of Young (MODY) via the PDX1 Gene

Citations

  • Ellard et al. 2008. PubMed ID: 18297260
  • Human Gene Mutation Database (Bio-base).
  • McDonald and Ellard. 2013. PubMed ID: 23878349
  • Owen. 2013. PubMed ID: 23760703
  • Prudente. 2015. PubMed ID: 26073777

Ordering/Specimens

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

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View Ordering Instructions

1) Select Test Method (Platform)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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