Familial Transthyretin Amyloidosis
- GTR Test IDHelpEach Test is a specific, orderable test from a particular laboratory, and is assigned a unique GTR accession number. The format is GTR00000001.1, with a leading prefix 'GTR' followed by 8 digits, a period, then 1 or more digits representing the version. When a laboratory updates a registered test, a new version number is assigned.: GTR000021486.6
- Last updated: 2023-02-08
- Test version history
Clinical testHelpIn the U.S., clinical tests must be performed under CLIA certification. When a lab uses the same methods for a test in both clinical and research settings, the test appears as two separate GTR records. for Amyloidogenic transthyretin amyloidosis
Offered by Molecular Genetics Laboratory
Overview
Test name
HelpThe name the laboratory assigns the test. Used as the default title of the page specific to the test.Familial Transthyretin Amyloidosis (TTR)
This is a clinical test intended for HelpPurposes or indications for the test. Lab-provided.: Diagnosis, Drug Response, Mutation Confirmation, Pre-symptomatic, Predictive, Prognostic
Click Indication tab for more information.
Please print requisition from website and ensure it is signed by the referring physician
Order URL HelpLink to the laboratory webpage with information about how to order this test. Please note that clicking on this link will open a new tab in your internet browser.: http://www.lhsc.on.ca/palm/molecular.html
Specimen source
Methodology
HelpThe assay's major method category (biochemical, cytogenetic or molecular genetics); method category (i.e. enzyme assay, chromosome breakage studies, targeted mutation analysis); methodology (i.e. the name of the method used) and instruments used when performing this test.- 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
Establish or confirm diagnosis
Guidance for management
Predictive risk information for patient and/or family members
Clinical validity
HelpHow consistently and accurately the test detects or predicts the intermediate or final outcomes of interest. Lab-provided.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
HelpThe lab's suggested sequence of ordering tests based on clinical scenarios. It may include information on: reflex testing including each test component, and scenarios which prompt additional components of testing; whether lab communicates interim results or automatically proceeds to further analyses; and if any components are performed in another laboratory.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
HelpLaboratory's order or catalog code for the test (used in the order requisition form).- Clinical Testing/Confirmation of Mutations Identified Previously
- Confirmation of research findings
- Custom Prenatal Testing
- Custom mutation-specific/Carrier testing
- Berk et al., 2013Repurposing diflunisal for familial amyloid polyneuropathy: a randomized clinical trial.
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