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Myotonia Congenita via the CLCN1 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
CLCN1 81406 81406,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11179CLCN181406 81406,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information.

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).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

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

  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Myotonia congenita (MC) is characterized by muscle stiffness in the legs, arms, and sometimes in the face, eyelids and tongue (Lossin et al. 2008). The muscle stiffness can be alleviated by brief exercise (known as the “warm-up” phenomenon). This is different from paramyotonia, a disease manifesting worse stiffness after exercise. Most patients with MC have hypertrophic muscles. The severity of the clinical symptoms is associated with the inheritance mode of the disease. In general, patients with autosomal recessive form of MC may have more severe symptoms.The onset of symptoms is variable, usually in infancy or childhood with some rare cases where onset may be as late as in patients’ 30s or 40s.

Patients with MC may be at an increased risk for adverse anesthesia-related events, therefore anesthesia should be used with caution (Bandschapp et al. 2013).

Genetics

MC can be inherited in an autosomal dominant (AD, also known as Thomsen disease) or autosomal recessive (AR, also known as Becker disease) manner (Dunø et al. 2005). Cases of semi-dominant inheritance, i.e., a homozygote manifests more severe phenotypes than a heterozygote, have also been reported (Kuo et al. 2006; Lin et al. 2006).

Myotonia congenita is caused by pathogenic variants in CLCN1 (Abdalla et al. 1992). The CLCN1 gene encodes the voltage-gated chloride channel ClC-1, which is highly expressed in the sarcolemma in skeletal muscle. The main function of ClC-1 is to regulate cellular excitability and to stabilize the resting potential (Pedersen et al. 2016). Pathogenic variants in CLCN1 gene can cause muscle fibers to show abnormally exaggerated response to stimulation. To date, over 260 different pathogenic variants have been identified, and more than 70% of them are missense or nonsense (Human Gene Mutation Database). The majority of the CLCN1 variants are associated with AR myotonia, whereas some variants have been found in both AD and AR form of the disease (Dunø et al. 2005). Pathogenic variants associated with dominant myotonia are mainly located in exon 8 (Fialho et al. 2007).

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity of this test is expected to be high, because CLCN1 is the only known causative gene for classical myotonia congenita. More than 95% of pathogenic variants causing myotonia congenita (both autosomal dominant and recessive) can be detected by this test (Dunø et al. 2005).

Testing Strategy

This test provides full coverage of all coding exons of the CLCN1 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

Individuals with the following clinical findings may consider this test: episodes of myotonia (muscle stiffness) or cramps beginning from childhood, myotonia that might be alleviated by brief exercise, myotonia induced by percussion of muscles, or a family history of autosomal dominant or recessive form of myotonia. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CLCN1.

Gene

Official Gene Symbol OMIM ID
CLCN1 118425
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Abdalla J.A. et al. 1992. American Journal of Human Genetics. 51: 579-84. PubMed ID: 1386711
  • Bandschapp O., Iaizzo P.A. 2013. Paediatric Anaesthesia. 23: 824-33. PubMed ID: 23802937
  • Dun° M. et al. 2005. Myotonia Congenita. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews« [Internet]. Seattle (WA): University of Washington, Seattle. PubMed ID: 20301529
  • Fialho D. et al. 2007. Brain. 130: 3265-74. PubMed ID: 17932099
  • Human Gene Mutation Database (Bio-base).
  • Kuo H-C. et al. 2006. Acta Neurologica Scandinavica. 113: 342-6. PubMed ID: 16629771
  • Lin M-J. et al. 2006. Biochemical and Biophysical Research Communications. 351: 1043-7. PubMed ID: 17097617
  • Lossin C. 2008. Advances in Genetics. 63: 25-55. PubMed ID: 19185184
  • Pedersen T.H. et al. 2016. The Journal of General Physiology. 147: 291-308. PubMed ID: 27022190

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)


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2) Select Additional Test Options

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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