TTR rs544924827: Understanding the V122I Variant
The TTR rs544924827 variant, commonly referred to as V122I, is a genetic change in the TTR gene associated with an increased risk of hereditary transthyretin amyloidosis. This condition involves the buildup of abnormal protein deposits, particularly affecting the heart in older individuals of African ancestry.
What each genotype means
Typical TTR profile
This is the most common genotype, representing the standard version of the TTR gene. Individuals with this genotype do not carry the V122I variant associated with hereditary transthyretin amyloidosis.
Carried by approximately 96-97% of individuals of African ancestry.
Increased amyloidosis risk
This genotype indicates you carry one copy of the V122I variant (also known as p.Val142Ile). This variant is associated with an increased risk of late-onset hereditary transthyretin amyloid cardiomyopathy, a condition where protein deposits can affect heart function. Please discuss your cardiovascular health and any family history of heart conditions with your clinician.
Carried by approximately 3-4% of individuals of African ancestry.
Elevated amyloidosis risk
This genotype indicates you carry two copies of the V122I variant (also known as p.Val142Ile). This variant is associated with an increased risk of late-onset hereditary transthyretin amyloid cardiomyopathy. Because this is an autosomal dominant condition, you should consult with a cardiologist or genetic counselor to discuss your heart health and potential screening options.
This genotype is rare, observed in a small subset of individuals within the carrier population.
What is the rs544924827 Variant?
The variant rs544924827, widely known in medical literature as V122I (or p.Val142Ile), is a specific change in the DNA sequence of the TTR gene. In this variant, the amino acid valine is replaced by isoleucine at position 122 of the mature transthyretin protein. This genetic alteration is categorized as a pathogenic or likely pathogenic variant, meaning it is known to contribute to the development of specific health conditions. It is primarily studied for its role in hereditary transthyretin amyloidosis, a condition where the transthyretin protein becomes unstable, misfolds, and forms amyloid fibrils that deposit in various tissues throughout the body. Because this variant is inherited in an autosomal dominant pattern, an individual only needs to inherit one copy of the variant allele from a parent to be at risk for the associated clinical manifestations.
The Role of the TTR Gene
The TTR gene provides instructions for making a protein called transthyretin. This protein is primarily produced in the liver and is responsible for transporting the thyroid hormone thyroxine and retinol (vitamin A) through the bloodstream. Under normal conditions, transthyretin exists as a stable tetramer, a structure composed of four identical subunits. However, when mutations like V122I occur, the stability of this tetrameric structure is compromised. The protein may dissociate into monomers or dimers, which are prone to misfolding and aggregating into insoluble amyloid fibrils. These fibrils can accumulate in organs such as the heart, peripheral nerves, and other tissues, potentially interfering with normal organ function. While the TTR protein is essential for transport, the structural changes caused by this variant can lead to the progressive deposition of amyloid, which is the hallmark of hereditary transthyretin amyloidosis.
Research and Clinical Associations
Research has established a strong association between the V122I variant and cardiac amyloidosis, particularly in individuals of African descent. Studies indicate that the clinical penetrance of this variant is age-dependent, meaning that symptoms are rarely observed before the age of 65. After this age, carriers of the variant show a significantly higher frequency of congestive heart failure and increased mortality compared to non-carriers. The condition is often underdiagnosed because its symptoms, such as heart failure, can mimic other more common cardiovascular diseases. Because the clinical presentation can be heterogeneous and the onset is typically late in life, medical professionals emphasize the importance of considering this genetic factor in patients presenting with unexplained heart failure or signs of cardiac amyloidosis. Evidence for this association is considered moderate to strong in the context of clinical genetics, as it is a well-documented cause of hereditary cardiac amyloidosis.
Population Frequency
The V122I variant is notably more common in individuals of African ancestry compared to other populations. Epidemiological studies have consistently estimated that approximately 3% to 4% of African Americans carry at least one copy of this variant allele. This relatively high frequency makes it a significant genetic factor to consider within this demographic. In contrast, the variant is rare or absent in many other global populations. Because of this specific distribution, genetic screening and awareness are particularly relevant for individuals of African descent who may have a family history of heart disease or unexplained cardiac symptoms. Understanding this population-specific frequency is crucial for clinicians when evaluating the likelihood of hereditary transthyretin amyloidosis in their patients.
What This Information Means for You
Knowing your status regarding the rs544924827 variant can provide important insights into your health risks, but it is not a diagnosis of disease. If you are aware that you carry this variant, it is essential to discuss this information with a healthcare provider or a genetic counselor. They can help interpret what this means for your specific health profile and determine if any proactive monitoring, such as regular cardiac evaluations, is appropriate for you. It is important to remember that genetic risk factors do not act in isolation; lifestyle, environment, and other genetic factors also play a role in health outcomes. Never make changes to your medical care or medication regimen based on genetic information without consulting your clinician or pharmacist. They are the best resources for translating genetic data into actionable, personalized medical advice.
How common is this variant?
The V122I variant is found in approximately 3-4% of individuals of African ancestry, while it is rare in other populations.
Frequently asked questions
Is the V122I variant a diagnosis of heart disease?
No, carrying the V122I variant is not a diagnosis of heart disease. It is a genetic risk factor that may increase the likelihood of developing cardiac amyloidosis, but not everyone with the variant will develop symptoms.
At what age do symptoms usually appear?
Symptoms associated with the V122I variant are typically age-dependent and are rarely seen before the age of 65. Clinical manifestations often become more apparent in individuals over the age of 70.
Should I get tested for this variant?
Genetic testing should be discussed with a healthcare provider or a genetic counselor. They can help determine if testing is appropriate based on your personal and family medical history.
Can this variant be treated?
There are medical management strategies and therapies available for hereditary transthyretin amyloidosis. You should discuss potential treatment options and monitoring with a cardiologist or a specialist in amyloidosis.
Sources & further reading
Educational information only, last refreshed 10/2/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Prevalent founder variant (p.Val142Ile) predisposing individuals of African ancestry to late-onset hereditary transthyretin amyloid cardiomyopathy.
Causes the classic p.Val50Met (historically Val30Met) pathogenic substitution responsible for familial amyloid polyneuropathy and hereditary transthyretin amyloidosis (ATTR).
Transthyretin missense variant p.Val142Ile (V122I) associated with hereditary transthyretin amyloid cardiomyopathy.
Pathogenic missense variant (p.Val142Ile / V122I) in TTR responsible for hereditary transthyretin amyloid cardiomyopathy.
Pathogenic missense variant (commonly designated Val30Met or p.Val50Met) associated with hereditary transthyretin-mediated amyloidosis.