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Maturity Onset Diabetes of the Young (MODY) and Permanent Neonatal Diabetes Mellitus (PNDM) via the INS 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
INS 81404 81404,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
15167INS81404 81404,81479 $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


  • 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; McDonald et al. 2013). 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 optimal treatment decisions, prognosis, family screening and obstetric management of gestational diabetes (Ellard et al. 2008). MODY has been conventionally classified into 11 types in terms of causative genes (Molven et al. 2011). Heterozygous INS pathogenic variants are a rare cause of MODY.

Within the spectrum of neonatal diabetes mellitus, permanent neonatal diabetes mellitus (PNDM) represents the severe end of hyperglycemia. In addition to neonatal diabetes, PNDM patients have neurological complications including developmental delay, epilepsy, cerebellar hypoplasia, learning difficulties, sensorineural deafness, and visual impairment (Molven et al. 2011). INS pathogenic variants are a major cause of PNDM through an autosomal dominant or recessive inheritance (Støy et al. 2007; Garin et al. 2010). Patients with recessive INS variants had a lower birth weight and were diagnosed earlier compared to those with dominant INS pathogenic variants (Garin et al. 2010).


The INS gene (2 coding exons) encodes insulin, the hormone regulating blood glucose level. Dominant-acting INS pathogenic variants cause both MODY and PNDM due to proinsulin misfolding while recessive-acting pathogenic variants cause PNDM due to reduced synthesis of the preproinsulin peptide (Meur et al. 2010; Støy et al. 2007; Garin et al. 2010).

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), and the ATP-sensitive potassium (KATP) channels (ABCC8 and KCNJ11) (Ellard et al. 2008; McDonald et al. 2013). INS pathogenic variants cause MODY10 (Molven et al. 2008; Meur et al. 2010). Heterozygous INS pathogenic variants found in MODY so far only include missense changes (Human Gene Mutation Database).

INS-PNDM can be inherited dominantly or recessively (Støy et al. 2007; Garin et al. 2010). Genetic defects of INS found in PNDM so far include missense, nonsense, regulatory, splicing mutations, small indels and large deletions (Human Gene Mutation Database). The other two major causative genes for PNDM are ABCC8 and KCNJ11 (Molven et al. 2011).

Clinical Sensitivity - Sequencing with CNV PG-Select

INS defects are a rare cause of MODY (Molven et al. 2011). The INS mutation detection rate in a large cohort of MODY patients is unknown because these mutations were only reported in a limited number of patients. In 279 patients with PNDM, the frequency of KCNJ11, ABCC8, and INS gene mutations was 31, 10, and 12%, respectively (Edghill et al. 2008).

Testing Strategy

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

This test provides full coverage of all coding exons of the INS gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for this test are patients with MODY or PNDM. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in INS.


Official Gene Symbol OMIM ID
INS 176730
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


  • Edghill EL. et al. 2008. Diabetes. 57: 1034-42. PubMed ID: 18162506
  • Ellard S. et al. 2008. Diabetologia. 51: 546-53. PubMed ID: 18297260
  • Garin I. et al. 2010. Proceedings of the National Academy of Sciences of the United States of America. 107: 3105-10. PubMed ID: 20133622
  • Human Gene Mutation Database (Bio-base).
  • McDonald T.J., Ellard S. 2013. Annals of Clinical Biochemistry. 50: 403-15. PubMed ID: 23878349
  • Meur G. et al. 2010. Diabetes. 59: 653-61. PubMed ID: 20007936
  • Molven A. et al. 2008. Diabetes. 57: 1131-5. PubMed ID: 18192540
  • Molven A., Njølstad PR. 2011. Expert Review of Molecular Diagnostics. 11: 313-20. PubMed ID: 21463240
  • Owen KR. 2013. Clinical Medicine (London, England). 13: 278-81. PubMed ID: 23760703
  • Støy J. et al. 2007. Proceedings of the National Academy of Sciences of the United States of America. 104: 15040-4. PubMed ID: 17855560


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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2) Select Additional Test Options

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