TTR rs28933979: Understanding the Val30Met Variant
The rs28933979 variant in the TTR gene, historically referred to as p.Val30Met, is a well-documented genetic change associated with hereditary transthyretin amyloidosis (ATTRv). This condition involves the buildup of abnormal protein deposits in the body, which can lead to systemic health issues.
What each genotype means
Typical TTR gene profile
This genotype represents the common, non-pathogenic version of the TTR gene. It is not associated with the development of hereditary transthyretin amyloidosis (ATTRv).
This is the most common genotype found in the general population globally.
Increased risk of amyloidosis
This genotype indicates the presence of one copy of the p.Val50Met (historically Val30Met) variant. Because this condition is inherited in an autosomal dominant manner, individuals with this genotype are at risk for developing hereditary transthyretin amyloidosis (ATTRv), a condition that can affect the peripheral nervous system and heart. Please discuss your clinical history and any symptoms with a healthcare provider or genetic counselor.
This genotype is very rare globally, though it is found at higher frequencies in specific founder populations in northern Portugal, northern Sweden, and Japan.
High risk of amyloidosis
This genotype indicates the presence of two copies of the p.Val50Met (historically Val30Met) variant. Research indicates that individuals with this genotype are highly likely to develop TTR-related familial amyloid polyneuropathy, with symptoms often appearing by age 80, though the age of onset can vary significantly. Please consult with a medical specialist to discuss appropriate monitoring and potential management strategies.
This genotype is extremely rare and is primarily identified within specific families or endemic clusters where the variant is prevalent.
What is the rs28933979 Variant?
The rs28933979 variant is a specific change in the DNA sequence of the TTR gene, located on chromosome 18. In scientific literature, this variant is frequently identified by the protein-level change it causes, known as p.Val30Met (or p.Val50Met depending on the nomenclature used). This means that at a specific position in the transthyretin protein, the amino acid valine is replaced by methionine. This single-letter change in the genetic code can alter the stability of the resulting protein, potentially causing it to misfold and aggregate into amyloid fibrils. These fibrils can deposit in various tissues throughout the body, particularly in the peripheral nerves and the heart, which is the hallmark of the associated condition, hereditary transthyretin amyloidosis (ATTRv).
The Role of the TTR Gene
The TTR gene provides the instructions for the body to produce a protein called transthyretin. This protein is primarily synthesized in the liver and circulates in the bloodstream. Its main biological function is to act as a transport vehicle, carrying thyroxine (a thyroid hormone) and retinol (vitamin A) throughout the body. Under normal conditions, transthyretin exists as a stable tetramer, a complex made of four identical protein subunits. When the TTR gene contains certain pathogenic variants, the resulting transthyretin protein may become unstable. This instability makes the protein more likely to break apart and misfold. These misfolded proteins can then clump together to form amyloid deposits, which interfere with the normal function of organs and tissues, leading to the clinical manifestations observed in ATTRv.
Research and Clinical Associations
Research has established a strong association between the rs28933979 variant and hereditary transthyretin amyloidosis. It is considered one of the most common pathogenic variants linked to this condition globally. The disease is inherited in an autosomal dominant pattern, meaning an individual only needs to inherit one copy of the variant from a parent to be at risk for developing the condition. However, the clinical presentation is highly variable, and the condition is characterized by incomplete penetrance, meaning not everyone who carries the variant will develop symptoms. Symptoms often include peripheral neuropathy, which affects sensation and movement, and autonomic dysfunction. Because the disease progression and age of onset can vary significantly even among family members, researchers continue to study the environmental and genetic factors that influence how this variant manifests in different individuals.
Population Frequency and Distribution
The rs28933979 variant is considered very rare in the general global population. However, it is not distributed evenly across the world. There are well-documented endemic clusters where the variant is found at higher frequencies, specifically in northern Portugal, northern Sweden, and parts of Japan. In these regions, the variant has been passed down through generations within specific family lines. Outside of these founder populations, the variant is identified much less frequently. Because of its rarity, population-wide screening is not standard practice. Individuals who have a family history of amyloidosis or unexplained neurological symptoms are typically the ones who undergo genetic testing to identify the presence of this specific TTR variant.
Managing Genetic Information
If you or a family member have been identified as a carrier of the rs28933979 variant, it is important to understand that this information is complex and requires professional interpretation. Genetic testing results should always be discussed with a qualified healthcare provider, such as a genetic counselor or a specialist in amyloidosis. They can help explain what the result means for your health and the health of your family members. Because the condition is associated with variable penetrance and late-onset symptoms, a positive result does not guarantee that you will develop the disease, nor does it predict the exact severity or timing of symptoms. You should never make medical decisions or changes to your health regimen based solely on genetic data without consulting your clinician. They can provide appropriate monitoring, discuss potential clinical trials, and offer guidance on managing any symptoms that may arise.
How common is this variant?
The rs28933979 variant is very rare globally (MAF <0.0001 in gnomAD), though it is found in endemic founder clusters in northern Portugal, northern Sweden, and Japan.
Frequently asked questions
What is the difference between Val30Met and rs28933979?
They refer to the same genetic variant. Val30Met is the historical name based on the amino acid change in the protein, while rs28933979 is the unique identifier used in modern genetic databases.
Does having the rs28933979 variant mean I will get sick?
Not necessarily. While this variant is associated with hereditary transthyretin amyloidosis, the condition has incomplete penetrance, meaning some carriers may never develop symptoms or may have a very late onset.
How is this variant inherited?
It is inherited in an autosomal dominant pattern. This means that an individual who carries the variant has a 50% chance of passing it on to each of their children.
Can I be tested for this variant?
Yes, genetic testing for the TTR gene is available. If you are concerned about your risk due to family history, you should speak with a doctor or a genetic counselor to discuss whether testing is appropriate for you.
Sources & further reading
Educational information only, last refreshed 9/21/2026. 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.
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.
Causes hereditary transthyretin amyloidosis (V122I), common in African Americans.