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GTR Home > Tests > Familial Transthyretin Amyloidosis


Test order codeHelp: TTR

Test name


Familial Transthyretin Amyloidosis (TTR)

Purpose of the test


This is a clinical test intended for Help: Diagnosis, Drug Response, Mutation Confirmation, Pre-symptomatic, Predictive, Prognostic



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How to order


Please print requisition from website and ensure it is signed by the referring physician
Order URL Help: http://www.lhsc.on.ca/palm/molecular.html

Specimen source

Cell culture
Isolated DNA
Peripheral (whole) blood


Molecular Genetics
DDeletion/duplication analysis
Next-Generation (NGS)/Massively parallel sequencing (MPS)
  • Illumina MiSeq/NextSeq
SMutation scanning of the entire coding region
Next-Generation (NGS)/Massively parallel sequencing (MPS)
  • Illumina MiSeq/NextSeq
ESequence analysis of select exons
Bi-directional Sanger Sequence Analysis
  • Applied Biosystems 3730 capillary sequencing instrument

Summary of what is tested

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Clinical utility


Establish or confirm diagnosis

Guidance for management

Predictive risk information for patient and/or family members

Clinical validity


Transthyretin (TTR) is an evolutionarily conserved serum and cerebrospinal fluid (CSF) protein that transports holo-retinol-binding protein (RBP; 180250) and thyroxine (T4). It is a homotetrameric protein synthesized mainly in liver, choroid plexus, retinal pigment epithelium, and pancreas. Mutant and wildtype TTR give rise to various forms of amyloid deposition (amyloidosis), originally defined pathologically by the formation and aggregation of misfolded proteins which result in extracellular deposits that impair organ function. The clinical syndromes associated with TTR aggregation are familial amyloid polyneuropathy (FAP) and cardiomyopathy (FAP), in which mutant TTR protein aggregates in peripheral and autonomic nerves and heart, respectively; and senile systemic amyloidosis (SSA), a late-onset disorder in which wildtype protein deposits primarily in heart, but also in gut and carpal tunnel

Testing strategy


All coding exons and 20 bp of flanking intronic sequence are enriched using an LHSC custom targeted hybridization protocol (Roche Nimblegen), followed by high throughput sequencing (Illumina). Sequence variants and copy number changes are assessed and interpreted using clinically validated algorithms and commercial software (SoftGenetics: Nextgene, Geneticist Assistant, Mutation Surveyor; and Alamut Visual). All exons have >1000x mean read depth coverage, with a minimum 200x coverage at a single nucleotide resolution. This assay meets the sensitivity and specificity of combined Sanger sequencing and MLPA copy number analysis. All variants interpreted as either ACMG category 1, 2, or 3 (pathogenic, likely pathogenic, VUS; PMID: 25741868) are confirmed using Sanger sequencing, MLPA, or other assays. ACMG category 4 and 5 variants (likely benign, benign) are not reported, but are available upon request. 000 Please print requisition from website and ensure it is signed by the referring physician

Test services

  • Clinical Testing/Confirmation of Mutations Identified Previously
  • Confirmation of research findings
  • Custom Prenatal Testing
  • Custom mutation-specific/Carrier testing

Suggested reading

  • Berk et al., 2013
    Repurposing diflunisal for familial amyloid polyneuropathy: a randomized clinical trial.

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