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Amyotrophic Lateral Sclerosis and Frontotemporal Dementia via the TBK1 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
10485 TBK1 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
10485TBK181479 81479,81479 $990 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

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

Testing run on PG-Select capture probes does not include exome-wide CNV analysis. Reflex is available to PGxome or an exome-based panel, or you can use this gene list to create a custom panel (click here).

Click here for costs to reflex to whole PGxome.

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

  • Sali Farhan, PhD

Clinical Features and Genetics

Clinical Features

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by a selective loss of motor neurons in the motor cortex, brain steam, and spinal cord (Tandan and Bradley. 1985. PubMed ID: 4051456). The dysfunction and loss of these neurons results in rapid progressive muscle weakness, atrophy and ultimately paralysis of limb, bulbar and respiratory muscles. The mean age of onset of symptoms is about 55 years of age; most cases begin between 40 and 70 years of age. The annual incidence of ALS is 1-2 per 100,000 (Cleveland and Rothstein. 2001. PubMed ID: 11715057).

The most common symptoms include twitching and cramping of muscles of the hands and feet, loss of motor control in the hands and arms, weakness and fatigue, tripping and falling. Symptoms usually begin with asymmetric involvement of the muscles. As the disease progresses, symptoms may include difficulty in talking, breathing and swallowing, shortness of breath, and paralysis.

Cognitive impairment was not been initially associated with ALS. However, frontotemporal dementia (FTD) has been reported in several cases. Dementia now has been documented in patients with ALS from different ethnic groups and affects both males and females (Wikström et al. 1982. PubMed ID: 7125994; Lipton et al. 2004. PubMed ID: 15351890; Mitsuyama and Inoue. 2009. PubMed ID: 19780984).

Genetics

About 10% of ALS cases are familial (Emery and Holloway. 1982. PubMed ID: 7180680). In most of these families, ALS is inherited in an autosomal dominant manner (AD-ALS) and shows age-dependent penetrance. In rare families, the disease is transmitted in an autosomal recessive or dominant X-linked pattern.

About 90% of patients with ALS are sporadic cases (SALS) with no known affected relatives. It is unclear how many of the apparently sporadic cases are inherited with low penetrance. The clinical presentations of familial ALS (FALS) and sporadic ALS (SALS) are similar. However, the onset of symptoms in FALS is usually earlier compared to that of SALS (Kinsley et al. 1993. PubMed ID: 20301623).

Autosomal Dominant ALS (AD-ALS) is a clinically and genetically heterogeneous disorder that affects all ethnic groups. Several genes have been implicated in the disease. They include C9orf72, SOD1, FUS, TARDBP, ANG, OPTN, VCP, VAPB, PFN1, MATR3, CHCHD10, ANG, and TBK1.

Pathogenic variants in the TBK1 gene have been implicated in ALS, FTD and ALS/FTD (Cirulli et al. 2015. PubMed ID: 25700176; Le Ber. 2015. PubMed ID: 26476236; van der Zee. 2017. PubMed ID: 28008748). Over 100 pathogenic variants have been reported to date. About half of the variants are missense; the other half is predicted to be truncating. Variants have been reported in both sporadic and familial cases (Freischmidt et al. 2017. PubMed ID: 27892983).

The TBK1 gene encodes TANK Binding Kinase 1, which is involved in several cellular processes including oncogenesis and immunological autophagy (Clément et al. 2008. PubMed ID: 19160540; Pilli et al. 2012. PubMed ID: 22921120).

Clinical Sensitivity - Sequencing with CNV PG-Select

Pathogenic variants in the TBK1 gene were detected in about 3.6% of ALS-FTD cases, 1.3% of ALS cases, and 0.4% of FTD cases (van der Zee et al. 2017. PubMed ID: 28008748).

Testing Strategy

This test provides full coverage of all coding exons of the TBK1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

All patients with symptoms suggestive of ALS, FTD, or ALS/FTD and no pathogenic variants in the previously identified ALS genes.

Gene

Official Gene Symbol OMIM ID
TBK1 604834
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Name
Amyotrophic Lateral Sclerosis / Motor Neuron Disease via the ANXA11 Gene
Amyotrophic Lateral Sclerosis / Motor Neuron Disease via the FUS Gene
Amyotrophic Lateral Sclerosis via the ANG Gene
Amyotrophic Lateral Sclerosis via the OPTN Gene
Amyotrophic Lateral Sclerosis/Motor Neuron Disease via the PFN1 Gene
Amyotrophic Lateral Sclerosis/Motor Neuron Disease via the TARDBP Gene

Citations

  • Cirulli et al. 2015. PubMed ID: 25700176
  • Clément et al. 2008. PubMed ID: 19160540
  • Cleveland and Rothstein. 2001. PubMed ID: 11715057
  • Emery and Holloway. 1982. PubMed ID: 7180680
  • Freischmidt et al. 2017. PubMed ID: 27892983
  • Kinsley et al. 2015 PubMed ID: 20301623
  • Le Ber. 2015. PubMed ID: 26476236
  • Lipton et al. 2004. PubMed ID: 15351890
  • Mitsuyama and Inoue. 2009. PubMed ID: 19780984
  • Pilli et al. 2012. PubMed ID: 22921120
  • Tandan and Bradley. 1985. PubMed ID: 4051456
  • van der Zee. 2017. PubMed ID: 28008748
  • Wikström et al. 1982. PubMed ID: 7125994

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

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ORDER OPTIONS

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

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