TTR Gene Mutations, Genetic Testing and ATTR Amyloidosis
Variants in the TTR gene cause hereditary transthyretin amyloidosis (hATTR), in which the transthyretin protein comes apart and builds up as amyloid in the heart, nerves and other organs. It is autosomal dominant, so a parent with 1 disease-causing variant has a 50% chance of passing it to each child, and not everyone who inherits it gets sick. More than 130 disease-causing variants are known, and TTR gene sequencing reads all of them from one blood, saliva or cheek swab sample.
The TTR gene sits on chromosome 18q12.1, and its full name is transthyretin. Orphanet links TTR to 3 rare conditions and lists variants in the gene as a cause of all of them. Trial Friend's ATTR Amyloidosis (Transthyretin Amyloidosis) page lists TTR among the genes behind the condition. As of October 13, 2026, 9 recruiting or soon-opening trials on ClinicalTrials.gov name TTR as a gene.
Other symbols for TTR in gene databases: CTS, HsT2651.
What the TTR gene does
TTR makes transthyretin, a protein made mainly in the liver that carries vitamin A and the thyroid hormone thyroxine through the blood. To do this, 4 transthyretin proteins join into a unit called a tetramer.
Summarized from the TTR page on MedlinePlus Genetics, U.S. National Library of Medicine, checked September 29, 2026.
The most common TTR gene variants
Lab reports and older papers number the same variant 2 ways. Older papers count from after a short signal piece that is trimmed off the protein, and current reports count from the very start, so V122I and p.Val142Ile name the same variant, as do V30M and p.Val50Met (GeneReviews).
V122I (p.Val142Ile) is the most common TTR variant in the US. Large studies find it in about 3% to 4% of Black Americans, including 3.43% of 14,333 African Americans in a 2015 study (Jacobson et al., 2015). It mainly affects the heart and tends to appear late in life. In Alnylam's no-charge testing program, 3,299 of the 4,297 people who tested positive from 2017 to 2023 carried it (Singh et al., 2025).
V30M (p.Val50Met) is the variant behind the classic nerve form of the disease first described in Portugal and Japan. How often carriers get sick depends a great deal on where the family comes from. About 80% of carriers in Portugal have the disease by age 50, compared with 11% in Sweden (Adams et al., 2021).
T60A (p.Thr80Ala) is linked to families from northwest Ireland and often affects the heart as well as the nerves (Reilly et al., 1995; Sattianayagam et al., 2012).
TTR genetic testing: who should get it and how
US heart failure guidelines recommend TTR gene sequencing for everyone diagnosed with ATTR cardiomyopathy, even when the disease looks like the age-related wild-type form (Heidenreich et al., 2022). Expert recommendations also advise it for anyone with a progressive nerve disease that has no other explanation (Adams et al., 2021).
Relatives of someone with a known variant can usually be tested at no cost through Alnylam Act or AstraZeneca's NavigATTR. A clinician orders the test, and genetic counseling is included. Of 89,760 people tested through Alnylam Act, 4.8% had a disease-causing TTR variant, and among those with a confirmed family history the figure was 32.2% (Singh et al., 2025).
A positive result means risk, not a diagnosis. For carriers without symptoms, European cardiologists recommend starting regular heart and nerve checks 10 years before the age at which affected relatives got sick (Garcia-Pavia et al., 2021). The federal Genetic Information Nondiscrimination Act bars health insurers and employers from using genetic results, but it does not cover life, disability or long-term care insurance (NHGRI).
Read the full guide to TTR gene testing, with family stories, the screening schedule for carriers and state insurance protections.
TTR and ATTR Amyloidosis (Transthyretin Amyloidosis)
These condition pages list TTR among the genes behind the condition, checked against genetics references when each page was written.
One disease-causing variant can be enough to cause the condition, though not everyone who carries it develops symptoms.
Hereditary ATTR is a TTR variant (V122I is common in people of African ancestry); wild-type ATTR, with no TTR variant, is an acquired form seen mainly in older men.
TTR mutation clinical trials
These recruiting or soon-opening trials mention TTR as a gene in their title, summary, eligibility rules or keywords. Some want people with a variant in it, and others study it more broadly, which is why each trial's own words are shown. In cancer trials the gene change is usually one found in the tumor rather than one a person inherited.
9 trials, checked October 13, 2026. The list refreshes from ClinicalTrials.gov every few hours.
All conditions linked to TTR gene mutations
Orphanet records how each gene relates to each condition. Orphanet links TTR to 3 rare conditions and lists variants in the gene as a cause of all of them.
- Causes it. Disease-causing variants in this gene are a direct cause of the condition.
TTR genetic test results and what a variant can mean
Labs sort each variant they find into 5 groups, from pathogenic and likely pathogenic through uncertain significance to likely benign and benign. Only the first 2 are usually treated as the cause of a condition. A variant of uncertain significance, or VUS, is one without enough evidence either way yet, and labs can reclassify it as research builds.
A genetic counselor or your doctor can explain what a specific result means for you and your family. Our genetic testing guide covers the terms, and MedlinePlus Genetics from the National Library of Medicine has a plain-language page on TTR.
TTR gene questions
What does a TTR gene mutation mean?
A disease-causing variant in the TTR gene makes transthyretin, a protein made mostly in the liver, more likely to come apart and misfold into amyloid that builds up in the heart, nerves and other organs. This is hereditary ATTR amyloidosis. A positive test means a higher risk, not a diagnosis, and how likely a carrier is to get sick depends on the specific variant and the family.
Is TTR amyloidosis inherited?
The hereditary form is. It is autosomal dominant, so a parent with 1 disease-causing TTR variant has a 50% chance of passing it to each child, son or daughter. Wild-type ATTR amyloidosis, the age-related form seen mainly in older men, happens with a normal TTR gene and is not inherited.
Which TTR gene variants are most common in the US?
V122I, also written p.Val142Ile, is by far the most common. It is carried by about 3% to 4% of Black Americans and mainly affects the heart later in life. In Alnylam's no-charge testing program it accounted for 3,299 of 4,297 positive results from 2017 to 2023. V30M (p.Val50Met) and T60A (p.Thr80Ala) are among the others seen in US families.
How can I get TTR genetic testing for free?
Two sponsored programs, Alnylam Act and AstraZeneca's NavigATTR, cover TTR testing at no cost to the patient when a clinician orders it, and both include genetic counseling. A family history of hereditary ATTR is enough to qualify for either. NavigATTR requires the order to come from a cardiology, genetics or neurology clinician.
What is TTR gene sequencing?
It is a lab test that reads the DNA letters of the TTR gene from a blood, saliva or cheek swab sample. Every disease-causing variant found so far sits in exons 2, 3 or 4 of the gene, so sequencing those parts covers more than 130 known variants in one test.
What does the TTR gene do?
TTR makes transthyretin, a protein made mainly in the liver that carries vitamin A and the thyroid hormone thyroxine through the blood. To do this, 4 transthyretin proteins join into a unit called a tetramer. This summary follows MedlinePlus Genetics from the U.S. National Library of Medicine.
Are there clinical trials for people with TTR gene variants?
As of October 13, 2026, 9 recruiting or soon-opening trials on ClinicalTrials.gov name TTR as a gene. Each one is listed on this page with the words from the trial that mention the gene. ClinicalTrials.gov also lists 70 open trials for ATTR Amyloidosis (Transthyretin Amyloidosis), and Match Me on Trial Friend can check those against age, sex, location and treatment history.
What conditions are linked to the TTR gene?
Orphanet links TTR to 3 rare conditions and lists variants in the gene as a cause of all of them. They include ATTRV122I amyloidosis, ATTRV30M amyloidosis and Euthyroid dysprealbuminemic hyperthyroxinemia. Orphanet is the European rare disease database run by INSERM in Paris.
What does a TTR variant of uncertain significance mean?
A variant of uncertain significance, or VUS, is a change in the gene that labs don't yet have enough evidence to call disease-causing or harmless. It is not used on its own to diagnose a condition, and labs can reclassify it as research builds. A genetic counselor can explain what a specific result means for you and your family.
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Sources
- Gene and condition links from Orphadata (Orphanet, INSERM US14), used under CC BY 4.0, read October 13, 2026.
- Trials from ClinicalTrials.gov, read October 13, 2026.
- TTR gene, MedlinePlus Genetics, U.S. National Library of Medicine.
- Inheritance and gene notes from the Trial Friend condition pages above, each checked against genetics references.
- Transthyretin Amyloidosis, GeneReviews (NCBI Bookshelf)
- Adams D, et al. Expert consensus recommendations to improve diagnosis of ATTR amyloidosis with polyneuropathy
- Jacobson DR, et al. Prevalence of the amyloidogenic transthyretin (TTR) V122I allele in 14 333 African-Americans
- Singh A, et al. Effectiveness and Utility of Genetic Testing in Establishing a Diagnosis of Hereditary Transthyretin Amyloidosis
- Reilly MM, et al. Familial amyloid polyneuropathy (TTR ala 60) in north west Ireland
- Sattianayagam PT, et al. Cardiac phenotype and clinical outcome of familial amyloid polyneuropathy associated with transthyretin alanine 60 variant
- Heidenreich PA, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure
- Garcia-Pavia P, et al. Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases
- Alnylam Act hATTR Amyloidosis Sponsored Testing Program
- NavigATTR Sponsored Testing Program
- Genetic Discrimination and GINA, National Human Genome Research Institute
Other gene pages
The gene search covers every gene Orphanet links to a rare disease.