LDLR rs121908034: What Your Genotype Means
The rs121908034 variant is a rare genetic change located in the LDLR gene. It is associated with familial hypercholesterolemia, a condition characterized by significantly elevated levels of low-density lipoprotein (LDL) cholesterol in the blood.
What each genotype means
Typical LDLR genotype
This genotype represents the common, non-variant sequence at this position in the LDLR gene. It is not associated with the pathogenic changes linked to familial hypercholesterolemia at this specific site.
This is the most common genotype found in the general population across all ancestries.
Familial hypercholesterolemia carrier
This genotype indicates the presence of a pathogenic variant in the LDLR gene, which is associated with familial hypercholesterolemia. Individuals with this variant may experience impaired clearance of low-density lipoprotein (LDL) cholesterol from the blood, potentially leading to elevated cholesterol levels. Please discuss these results with a healthcare provider or a genetic counselor to understand your personal health context and appropriate management.
This specific genotype is rare and is not commonly observed in the general population.
Familial hypercholesterolemia risk
This genotype indicates the presence of two copies of the pathogenic variant, which is associated with a more severe presentation of familial hypercholesterolemia. This condition significantly impacts the body's ability to process cholesterol, often resulting in very high LDL levels from a young age. It is essential to consult with a medical specialist, such as a cardiologist or lipidologist, to discuss clinical monitoring and management strategies.
This genotype is extremely rare in the general population.
Understanding the Variant and Its Location
The variant rs121908034 is a specific change in the DNA sequence of the LDLR gene, which is located on chromosome 19. In scientific literature, this variant is sometimes referred to by other names, such as c.564C>G or the protein-level change Tyr167Ter (also written as Y188X). This specific mutation introduces a premature stop signal during the process of protein synthesis. Instead of creating a full-length, functional protein, the cellular machinery stops reading the genetic instructions early, resulting in a truncated and typically non-functional version of the LDL receptor. Because this change occurs within the coding region of the gene, it can significantly disrupt the normal biological function of the receptor, which is critical for maintaining healthy cholesterol levels in the body.
The Role of the LDLR Gene
The LDLR gene provides the instructions for making the low-density lipoprotein receptor protein. These receptors are found on the surface of cells, particularly in the liver, and act like specialized 'docking stations' for LDL particles circulating in the bloodstream. When LDL particles bind to these receptors, they are pulled into the cell through a process called endocytosis, where they are broken down and removed from the blood. This mechanism is essential for regulating the amount of cholesterol circulating in the body. When the LDLR gene is mutated, the body may produce fewer receptors or receptors that do not function correctly. This leads to a buildup of LDL cholesterol in the blood, which is a hallmark of familial hypercholesterolemia, a condition that can increase the risk of cardiovascular issues if left unmanaged.
Research and Clinical Associations
Research has consistently associated variants in the LDLR gene, including rs121908034, with familial hypercholesterolemia. The evidence for this association is considered strong, as this variant has been observed in individuals diagnosed with the condition. Studies have shown that this specific mutation leads to significantly reduced or absent protein expression and function compared to the normal, wild-type version of the receptor. Because familial hypercholesterolemia is often inherited in a semidominant pattern, the severity of the cholesterol elevation can depend on whether an individual carries one or two copies of a pathogenic variant. It is important to note that while this variant is linked to the condition, clinical diagnosis of familial hypercholesterolemia is based on a combination of factors, including blood lipid profiles, family history, and physical examination, rather than genetic testing alone.
Population Frequency
The rs121908034 variant is classified as rare across global population cohorts. Data from large-scale genomic databases, such as gnomAD, indicate that this specific mutation is not commonly found in the general population. Because it is a rare variant, it is not typically included in standard, broad-spectrum genetic screening panels unless specifically targeted for clinical diagnostic purposes. Its rarity means that most individuals will not carry this specific change. If you have received a report indicating the presence of this variant, it is essential to discuss the findings with a healthcare professional or a genetic counselor who can provide context based on your personal and family medical history.
Managing Your Genetic Information
Genetic information regarding variants like rs121908034 should be interpreted within the context of your overall health. If you are concerned about your cholesterol levels or a family history of heart disease, the most important step is to consult with a physician or a lipid specialist. They can order appropriate clinical blood tests to measure your actual cholesterol levels and determine if any medical intervention is necessary. You cannot diagnose yourself based on a genetic report, and you should never change or stop any prescribed medications without consulting your clinician or pharmacist. Genetic testing provides a piece of the puzzle, but clinical management is always guided by your current health status, lifestyle, and professional medical advice.
How common is this variant?
The rs121908034 variant is considered rare based on population cohorts in the Genome Aggregation Database (gnomAD).
Frequently asked questions
What is familial hypercholesterolemia?
Familial hypercholesterolemia is a genetic disorder that causes high levels of LDL cholesterol in the blood from a young age. It is caused by mutations in genes like LDLR that prevent the body from effectively removing cholesterol from the bloodstream.
Does having this variant mean I have high cholesterol?
Not necessarily, though it is a known risk factor. A genetic variant is only one piece of the puzzle, and you should have your cholesterol levels measured by a doctor to understand your actual health status.
Should I change my diet if I have this variant?
Dietary choices are important for heart health, but you should consult with your doctor or a registered dietitian before making significant changes. They can provide personalized advice based on your specific lipid profile and medical history.
Is this variant common?
No, rs121908034 is considered a rare variant. It is not found in the vast majority of the population.
What should I do if my report shows this variant?
You should share the report with your primary care physician or a cardiologist. They can help you interpret the results in the context of your health and determine if any follow-up testing or monitoring is needed.
Sources & further reading
Educational information only, last refreshed 10/7/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This pathogenic variant in the LDLR gene is a novel contributor to familial hypercholesterolemia, leading to significantly elevated LDL cholesterol levels.
This mutation is associated with familial hypercholesterolemia, leading to significantly elevated LDL cholesterol levels.
Causes high cholesterol from birth (Familial Hypercholesterolemia).
This SNP is a known pathogenic mutation contributing to severe hypercholesterolemia phenotypes.
A clinically significant variant in the LDLR gene associated with high LDL cholesterol levels.
This variant is associated with autosomal dominant familial hypercholesterolemia, affecting low-density lipoprotein receptor function.