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Deafness, Autosomal Dominant 20 (DFNA20) via the ACTG1 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
8973 ACTG1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8973ACTG181479 81479(x2) $890 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 backbone).

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

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

For Sanger Sequencing click here.

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

  • Ben Dorshorst, PhD

Clinical Features and Genetics

Clinical Features

Nonsyndromic hearing loss is characterized by difficulty or inability to hear that is not associated with any visible defects involving the external ear, other organs, or any other medical condition. Nonsyndromic hearing loss may be associated with abnormalities involving the middle ear and/or the inner ear (Ciuman 2013; Dodson et al. 2011; Hilgert et al. 2009). At least 70% of cases involving hearing loss are nonsyndromic (Van Camp et al. 1997).

Nonsyndromic hearing loss and deafness due to pathogenic variants in the ACTG1 gene is associated with postlingual, bilateral, moderate to profound, progressive sensorineural hearing impairment beginning in the high frequencies. No vestibular abnormalities are present (Zhu et al. 2003).

Genetics

DFNA20 is an autosomal dominant hearing disorder that is caused by pathogenic sequence variants in the actin gamma 1 (ACTG1) gene, which is located on chromosome 17q25.3. The ACTG1 gene spans 6.9 kb and consists of 5 coding exons that produce a 375 amino acid protein. The exact role of the ACTG1 protein in inner ear function remains unknown, although variants in many actin-interacting proteins are also known to cause hearing loss (Zhu et al. 2003).

Only missense variants in ACTG1 have been reported as pathogenic for hearing loss, with >15 variants reported to date in different families (Human Gene Mutation Database). Missense variants in ACTG1 have also been reported to cause Baraitser-Winter syndrome 2, characterized by distinct craniofacial features, ocular coloboma and neuronal migration defect (Rivière et al. 2012).

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity of this sequencing test is not precisely known. More than 15 missense variants in ACTG1 have been reported as pathogenic for hearing loss in different families (Human Gene Mutation Database). However, screening of 19 Norwegian and Danish families with autosomal dominant hearing loss did not identify any pathogenic variants in ACTG1 (Rendtorff et al. 2006), suggesting ACTG1 is not a common cause of autosomal dominant hearing loss. Analytical sensitivity should be high because all reported variants are detectable by sequencing.

Testing Strategy

This test provides full coverage of all coding exons of the ACTG1 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

Nonsyndromic hearing loss and deafness due to variants in the ACTG1 gene is suspected in individuals with the following: postlingual, bilateral, moderate to profound, progressive sensorineural hearing impairment beginning in the high frequencies; no related systemic findings identified by medical history and physical examination; and/or a family history of nonsyndromic hearing loss consistent with autosomal dominant inheritance.

Gene

Official Gene Symbol OMIM ID
ACTG1 102560
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Ciuman R.R. 2013. Medical Science Monitor. 19: 1195-210. PubMed ID: 24362017
  • Dodson K.M. et al. 2011. American Journal of Medical Genetics. Part A. 155A: 993-1000. PubMed ID: 21465647
  • Hilgert N. et al. 2009. Mutation Research. 681: 189-96. PubMed ID: 18804553
  • Human Gene Mutation Database (Bio-base).
  • Rendtorff N.D. et al. 2006. European Journal of Human Genetics. 14: 1097-105. PubMed ID: 16773128
  • Rivière J.B. et al. 2012. Nature Genetics. 44: 440-4, S1-2. PubMed ID: 22366783
  • Van Camp G. et al. 1997. American Journal of Human Genetics. 60: 758-64. PubMed ID: 9106521
  • Zhu M. et al. 2003. American Journal of Human Genetics. 73: 1082-91. PubMed ID: 13680526

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.
Total Price: $
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