LDLR rs121908740: What Your Genotype Means
The rs121908740 variant is a rare genetic change located in the LDLR gene. It is associated with familial hypercholesterolemia, a condition characterized by the impaired clearance of low-density lipoprotein (LDL) cholesterol from the blood.
What each genotype means
Typical LDL receptor function
This genotype represents the common, non-variant form of the LDLR gene at this position. It is not associated with the pathogenic effects linked to familial hypercholesterolemia. Individuals with this genotype should follow standard cardiovascular health guidelines.
This is the most common genotype found in the general population across all ancestries.
Increased cardiovascular risk
This genotype indicates the presence of one copy of the pathogenic variant, which is associated with familial hypercholesterolemia. This condition can lead to significantly elevated LDL cholesterol levels and an increased risk of premature cardiovascular disease. Please discuss these results with a healthcare provider or a lipid specialist to determine appropriate screening and management.
This genotype is extremely rare, occurring in less than 0.1% of the global population.
Severe cardiovascular risk
This genotype indicates the presence of two copies of the pathogenic variant, which is associated with a severe form of familial hypercholesterolemia. This biallelic state often results in markedly higher LDL cholesterol levels and a significantly elevated risk of early-onset heart disease compared to those with one copy. It is essential to consult with a medical professional for clinical evaluation and long-term cardiovascular management.
This genotype is exceptionally rare in the general population.
Understanding the Variant and Its Location
The rs121908740 variant is a specific single nucleotide polymorphism (SNP) found within the LDLR gene. This gene is located on chromosome 19, specifically at position 19p13.2. In the context of genetic research, variants like rs121908740 are identified by their unique reference SNP ID (rsID) to help scientists track their location and potential impact on human health. Because this variant is located within the coding region of the LDLR gene, it has the potential to alter the structure or function of the protein that the gene produces. Geneticists study these specific locations to understand how minor changes in the DNA sequence can lead to significant differences in biological processes, such as how the body manages cholesterol levels in the bloodstream.
The Role of the LDLR Gene
The LDLR gene provides instructions for making the low-density lipoprotein receptor (LDLR) protein. This receptor is essential for the body's ability to remove LDL cholesterol—often referred to as 'bad' cholesterol—from the circulation. The LDLR protein is primarily found on the surface of liver cells, where it binds to LDL particles and facilitates their uptake into the cell, where they are broken down. This process is a critical regulatory mechanism that keeps blood cholesterol levels within a healthy range. When the LDLR gene contains a pathogenic variant, the resulting receptor may be missing, reduced in number, or unable to function correctly. This leads to an accumulation of LDL cholesterol in the blood, which is a hallmark of familial hypercholesterolemia.
Research and Evidence Strength
Research into rs121908740 classifies it as a pathogenic missense variant associated with familial hypercholesterolemia. Familial hypercholesterolemia is an autosomal dominant disorder, meaning that inheriting a single copy of a pathogenic variant from one parent is typically sufficient to cause the condition. The evidence for this specific variant is grounded in clinical observations of individuals who exhibit the physical and biochemical traits of the disorder. However, the strength of evidence for any single variant can vary based on the amount of functional data available. While the association with high cholesterol is well-documented for the LDLR gene as a whole, the specific clinical impact of rare variants like rs121908740 is often determined through family studies and clinical diagnostic testing. It is important to note that genetic associations are statistical in nature and do not guarantee a specific health outcome for every individual.
Population Frequency
The rs121908740 variant is considered rare in global populations, with a frequency typically reported as less than 0.001 in large-scale genetic cohorts. Because it is so uncommon, it is not frequently observed in the general population. Rare variants are often identified through clinical screening of individuals who already present with symptoms of high cholesterol or premature cardiovascular disease. The low frequency of this variant underscores that it is not a common feature of the human genome but rather a specific genetic factor that may be present in certain families or populations. Because of its rarity, large-scale population studies may have limited data on its penetrance, which refers to the proportion of people with the variant who actually develop the associated clinical symptoms.
What You Can and Cannot Do With This Information
Genetic information regarding variants like rs121908740 is intended for educational purposes and should not be used for self-diagnosis or to make medical decisions. If you have received a report indicating you carry this variant, it is essential to discuss the findings with a qualified healthcare provider, such as a cardiologist or a genetic counselor. They can interpret the results in the context of your personal and family medical history, as well as your current cholesterol levels. A clinician can determine if further testing or specific management strategies are appropriate for your health. Never change or stop any prescribed medications based on genetic test results without consulting your doctor or pharmacist. Genetic testing is a tool to help inform clinical care, not a substitute for professional medical evaluation and treatment.
How common is this variant?
The rs121908740 variant is rare, with a frequency of less than 0.001 in global cohorts.
Frequently asked questions
What is familial hypercholesterolemia?
Familial hypercholesterolemia is an inherited condition that causes very high levels of LDL cholesterol in the blood. It is caused by mutations in genes like LDLR that prevent the body from effectively clearing cholesterol from the circulation.
Does having this variant mean I have high cholesterol?
Not necessarily. While this variant is associated with the condition, genetic testing is only one piece of the puzzle. You should consult a doctor to have your actual cholesterol levels measured and to discuss your overall cardiovascular risk.
Can I change my genotype?
No, your genotype is determined at conception and cannot be changed. However, lifestyle choices and medical treatments can often help manage the health risks associated with certain genetic variants.
Should I get tested for this variant?
Genetic testing for specific variants is usually recommended by a doctor if there is a strong family history of premature heart disease or very high cholesterol. You should discuss the necessity and implications of such testing with a healthcare professional.
Sources & further reading
Educational information only, last refreshed 9/20/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Pathogenic missense variant altering low-density lipoprotein receptor function and predisposing to severe familial hypercholesterolemia.
This pathogenic variant in the LDLR gene is a contributor to familial hypercholesterolemia, leading to significantly elevated LDL cholesterol levels.
Variant in the LDLR 3' UTR region associated with statin efficacy, often studied in East Asian cohorts.
A variant in the 3' UTR of the LDLR gene associated with variations in statin therapeutic response.
Synonymous variant in the LDLR gene associated with plasma LDL cholesterol levels.
This variant is a well-established marker associated with LDL cholesterol levels and risk of coronary artery disease.