Definition

Pathogenic variants in the TTR gene (18q12.1) destabilize the transthyretin protein produced in the liver, causing its tetramer structure to dissociate and form amyloid fibrils. These fibrils accumulate in the heart, peripheral nerves, and other tissues, causing cardiomyopathy and polyneuropathy; the most common variant is Val30Met (with high prevalence in Portuguese/Japanese clusters), while Val122Ile is associated with a cardiac phenotype in populations of African descent.

Gene/region examined

TTR - Exon 1, TTR - Exon 2, TTR - Exon 3, TTR - Exon 4

Method

Sequence analysis

Accepted sample types

EDTA blood, AF, CVS

Inheritance

Inherited, autosomal dominant (with variable penetrance and expressivity).

Related Tests

Inheritance Patterns

Describes how a genetic condition is passed on within a family. There are five main patterns

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Carrier (Heterozygous / Homozygous)

Why it matters: In autosomal recessive inheritance, when each parent is a carrier (while both appear healthy), the chance of their child being born with the disease is 25% in each

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VUS (Variant of Uncertain Significance)

This is the situation where the test has detected a change in the DNA, but the role of this change in the development of disease is unconfirmed.

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How to Read a Genetic Test Result (Positive / Negative / VUS)

A genetic test result falls into three main categories

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Types of Genetic Tests

A genetic test is a type of medical test that detects changes in genes, chromosomes or proteins. Today there are more than 77,000 genetic tests available.

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