TYK2 Deficiency via the TYK2 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
11781 TYK2 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11781TYK281479 81479(x2) $890 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 backbone).

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

Turnaround Time

18 days on average for standard orders or 13 days 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

Clinical Features and Genetics

Clinical Features

TYK2 deficiency is a very rare disorder that has only been described in two cases to date with both patients exhibiting increased susceptibility to infection. In one patient, the triad of HIES symptoms including elevated IgE, dermatitis, and staphylococcal infections were present (Minegishi et al. 2006). The second patient presented with normal IgE levels, but had Bacille Calmette-Guerin disease and Salmonella gastroenteritis by 15 years of age (Kilic et al. 2012). Susceptibility to infection is a common feature between the two patients, but other clinical findings were divergent. Therefore, the classic symptoms for TYK2 deficiency remain to be fully defined. Pathogenic variants in the TYK2 gene have also been associated with susceptibility to systemic lupus erythematosus and multiple sclerosis through genome wide association studies. The exact role of TYK2 pathogenic variants in those disorders is unknown (Ban et al. 2009; Couturier et al. 2011).

Genetics

TYK2 deficiency is inherited in an autosomal recessive manner through pathogenic variants in the TYK2 gene. This disorder has only been described in two patients with homozygous deletions leading to frameshifts and premature protein termination (Minegishi et al. 2006; Kilic et al. 2012). Missense variants in the TYK2 gene have been reported in patients with systemic lupus erythematosus and multiple sclerosis through large genome wide association studies (Ban et al. 2009; Couturier et al. 2011). Additional functional and genetic studies are still needed to confirm pathogenicity of TYK2 variants in those disorders. The TYK2 protein is a non-receptor Jak kinase family member that mediates downstream signaling from several cytokines, especially type I interferon, to spur host immunity (Prchal-Murphy et al. 2012).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity cannot be estimated because only a small number of patients have been reported. Analytical sensitivity should be high because all pathogenic variants reported to date are detected by sequencing.

Testing Strategy

This test provides full coverage of all coding exons of the TYK2 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 showing IgE levels higher than 2000 U/ml and a weighted score of clinical features >30 (Szczawinska-Poplonyk et al 2011). Individuals with recurrent infections and symptoms similar to HIES or Bacille Calmette-Guerin disease are ideal candidates. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in TYK2.

Gene

Official Gene Symbol OMIM ID
TYK2 176941
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Tyrosine Kinase 2 Deficiency AR 611521

Citations

  • Ban M, Goris A, Lorentzen \AAslaug R., Baker A, Mihalova T, Ingram G, Booth DR, Heard RN, Stewart GJ, Bogaert E, Dubois B, Harbo HF, Celius EG, Spurkland A, Strange R, Hawkins C, Robertson NP, Dudbridge F, Wason J, De Jager PL, Hafler D, Rioux JD, Ivinson AJ, McCauley JL, Pericak-Vance M, Oksenberg JR, Hauser SL, Sexton D, Haines J, Sawcer S; Wellcome Trust Case-Control Consortium (WTCCC), Compston A. 2009. Replication analysis identifies TYK2 as a multiple sclerosis susceptibility factor. European journal of human genetics 17: 1309–1313. PubMed ID: 19293837
  • Couturier N, Bucciarelli F, Nurtdinov RN, Debouverie M, Lebrun-Frenay C, Defer G, Moreau T, Confavreux C, Vukusic S, Cournu-Rebeix I, Goertsches RH, Zettl UK, Comabella M, Montalban X, Rieckmann P, Weber F, Müller-Myhsok B, Edan G, Fontaine B, Mars LT, Saoudi A, Oksenberg JR, Clanet M, Liblau RS, Brassat D. 2011. Tyrosine kinase 2 variant influences T lymphocyte polarization and multiple sclerosis susceptibility. Brain 134: 693–703. PubMed ID: 21354972
  • Kilic SS, Hacimustafaoglu M, Boisson-Dupuis S, Kreins AY, Grant AV, Abel L, Casanova J-L. 2012. A Patient with Tyrosine Kinase 2 Deficiency without Hyper-IgE Syndrome. The Journal of Pediatrics 160: 1055–1057. PubMed ID: 22402565
  • Minegishi Y, Saito M, Morio T, Watanabe K, Agematsu K, Tsuchiya S, Takada H, Hara T, Kawamura N, Ariga T, Kaneko H, Kondo N, Tsuge I, Yachie A, Sakiyama Y, Iwata T, Bessho F, Ohishi T, Joh K, Imai K, Kogawa K, Shinohara M, Fujieda M, Wakiguchi H, Pasic S, Abinun M, Ochs HD, Renner ED, Jansson A, Belohradsky BH, Metin A, Shimizu N, Mizutani S, Miyawaki T, Nonoyama S, Karasuyama H. 2006. Human Tyrosine Kinase 2 Deficiency Reveals Its Requisite Roles in Multiple Cytokine Signals Involved in Innate and Acquired Immunity. Immunity 25: 745–755. PubMed ID: 17088085
  • Prchal-Murphy M, Semper C, Lassnig C, Wallner B, Gausterer C, Teppner-Klymiuk I, Kobolak J, Müller S, Kolbe T, Karaghiosoff M, Dinnyés A, Rülicke T, Leitner NR, Strobl B, Müller M. 2012. TYK2 Kinase Activity Is Required for Functional Type I Interferon Responses In Vivo. PLoS ONE 7: e39141. PubMed ID: 22723949
  • Szczawinska-Poplonyk A, Kycler Z, Pietrucha B, Heropolitanska-Pliszka E, Breborowicz A, Gerreth K. 2011. The hyperimmunoglobulin E syndrome--clinical manifestation diversity in primary immune deficiency. Orphanet J Rare Dis 6: 76. PubMed ID: 22085750

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


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


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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