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Familial Amyloidosis (hATTR) via the TTR 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
TTR 81404 81404,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8983TTR81404 81404,81479 $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. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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.


Genetic Counselors


  • Jessica Tumolo, PhD

Clinical Features and Genetics

Clinical Features

Hereditary transthyretin amyloidosis (ATTR) is a protein misfolding disorder leading to deposition of amyloid aggregates resulting in organ dysfunction. ATTR is a slowly progressive disorder which presents in three main forms: neuropathic, leptomeningeal and cardiac. Neuropathic ATTR affects the peripheral and autonomic nervous system resulting in peripheral neuropathy and difficulty controlling bodily functions. Leptomeningeal ATTR affects the central nervous system causing hydrocephalus, ataxia, seizures and loss of intellectual function (Ando et al. 2013. PubMed ID: 23425518). Cardiac ATTR affects the heart resulting in arrhythmia, cardiomegaly or congestive heart failure. Symptom onset occurs in the third to fifth decade of life. ATTR affects about one in 100,000 individuals in the United States. Treatment of patients with ATTR includes possible transplantation, TTR stabilizer drugs, or TTR antisense therapies that reduce TTR synthesis (Adams et al. 2018. PubMed ID: 29972753; Benson et al. 2018. PubMed ID: 29972757; Ando et al. 2013. PubMed ID: 23425518). Genetic testing is helpful in distinguishing ATTR from other forms of amyloidosis and from other neuropathies and cardiomyopathies (Sekijima. 2018. PubMed ID: 20301373).  


Pathogenic variants in the TTR gene account for ~90% of hereditary amyloidosis cases and are inherited in an autosomal dominant manner with incomplete penetrance. Nearly all ATTR cases are inherited. Autosomal recessive ATTR has been reported in a few cases with patients having higher penetrance, severity and earlier onset compared to autosomal dominant cases (Sekijima. 2018. PubMed ID: 20301373). Other genes associated with hereditary amyloidosis include FGA, B2M, LYZ and APOA1.

Missense changes found throughout the TTR gene account for >95% of the causative variants. Specific missense changes are associated with neuropathic, cardiac or leptomeningeal amyloidosis forms, but phenotypic overlap can occur.

There are two primary founder variants c.148G>A (p.Val50Met) and c.424G>A (p.Val142Ile). These variants are also referred to as p.Val30Met and p.Val122Met using legacy nomenclature. The p.Val50Met variant has been found in 1 in 538 northern Portuguese with penetrance of 80% by age 50, 4% of northern Swedes with penetrance of 11% by age 50, and in 1 in 100,000 Nagano Japanese (Ando et al. 2013. PubMed ID: 23425518; Sekijima et al 2018. PubMed ID: 29343286). Neuropathic ATTR is primarily found in individuals with the p.Val50Met variant in early stages with cardiac and kidney dysfunction . Transgenic mice expressing the p.Val50Met variant present with amyloidosis leading to gastrointestinal, cardiac, and kidney dysfunction (Yi et al. 1991. PubMed ID: 1992765). The p.Val142Ile variant is found in ~3.5% of African Americans with age dependent penetrance and has been found in 10% of African Americans over 65 years of age with severe congestive heart failure (Buxbaum and Ruberg. 2017. PubMed ID: 28102864).

The TTR gene encodes transthyretin, which functions in transport of retinol (vitamin A) and thyroxine (thyroid hormone) when present as a homotetramer (Ando et al. 2013. PubMed ID: 23425518). The TTR gene is not essential for viability of tissue culture cells. Homozygous TTR knockout mice have decreased susceptibility to AMPA-induced neurodegeneration (Nunes et al. 2009. PubMed ID: 19595729).

Clinical Sensitivity - Sequencing with CNV PGxome

In a study of 79 unrelated cases meeting criteria for TTR hereditary amyloid polyneuropathy of Portuguese or French descent, pathogenic variants were identified in all cases. Portuguese ATTR patients all were heterozygous for the c.148G>A (p.Val50Met) variant with 87.8% cases having a positive family history. The c.148G>A variant was also identified in ~25% of French ATTR patients and was the most frequently identified pathogenic variant. In French ATTR patients, 43.5% had a positive family history (Planté-Bordeneuve et al. 2003. PubMed ID: 14627687). Analytical sensitivity is likely >99% as all reported pathogenic variants in the TTR gene are detectable by sequencing.

Testing Strategy

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

This test provides full coverage of all coding exons of the TTR 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 testing include individuals with a positive family history for amyloidosis and presenting with cardiac conduction blocks, cardiomyopathy, peripheral sensorimotor and/or motor neuropathy. Patients with tissue biopsies indicating amyloid deposits or anti-TTR antibodies are also good candidates for TTR gene sequencing (Sekijima. 2018. PubMed ID: 20301373).

Targeted testing for the c.148G>A (p.Val50Met) and c.424G>A (p.Val142Ile) founder variants is available. Testing may be appropriate for determining carrier status as pathogenic variants in the TTR gene exhibit incomplete penetrance. The reproductive partners of individuals who carry pathogenic variants in TTR are also candidates.


Official Gene Symbol OMIM ID
TTR 176300
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Amyloidogenic Transthyretin Amyloidosis AD 105210

Related Test

Hypertrophic Cardiomyopathy Panel


  • Adams et al. 2018. PubMed ID: 29972753
  • Ando et al. 2013. PubMed ID: 23425518
  • Benson et al. 2018. PubMed ID: 29972757
  • Buxbaum and Ruberg. 2017. PubMed ID: 28102864
  • Nunes et al. 2009. PubMed ID: 19595729
  • Planté-Bordeneuve et al. 2003. PubMed ID: 14627687
  • Sekijima. 2018. PubMed ID: 20301373
  • Yi et al. 1991 PubMed ID: 1992765


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