PKP2 rs193922674: What Your Genotype Means
The rs193922674 variant is a rare genetic change located in the PKP2 gene. It has been identified in clinical research as a pathogenic mutation associated with an increased risk of developing arrhythmogenic right ventricular cardiomyopathy (ARVC), a condition affecting the heart's structure.
What each genotype means
Typical genetic profile
This is the common, expected genotype for the PKP2 gene at this location. It is not associated with the increased risk of arrhythmogenic right ventricular dysplasia (ARVD) type 9 linked to this variant.
This is the most common genotype found in the general population.
Increased ARVD risk
This genotype, also known as c.2146-1G>C, is considered a pathogenic mutation associated with an increased risk of developing arrhythmogenic right ventricular dysplasia (ARVD) type 9. Because this condition is inherited in a dominant manner, individuals with this variant should consult with a cardiologist or genetic counselor to discuss appropriate cardiac screening and clinical management.
This is a rare genotype that is not commonly found in the general population.
Understanding the Variant
The variant rs193922674 is a specific change in the DNA sequence of the PKP2 gene, also known as c.2146-1G>C. It is located on chromosome 12 at position 32,802,557. In genetics, a single-nucleotide polymorphism (SNP) like this represents a variation at a single position in the DNA chain. While many variants are harmless, some can alter the instructions the body uses to build proteins. This particular variant is categorized as a pathogenic mutation in clinical databases, meaning it is linked to a specific health condition. Because it is rare, it is not commonly found in the general population, and its presence is typically investigated in the context of clinical heart health assessments.
The Role of the PKP2 Gene
The PKP2 gene provides the blueprint for creating a protein called plakophilin-2. This protein is a vital component of desmosomes, which are specialized structures that act like 'glue' to hold heart muscle cells (myocytes) together. By forming these strong junctions, desmosomes ensure the structural integrity of the myocardium, the muscular wall of the heart. When the PKP2 gene is altered, the resulting plakophilin-2 protein may not function correctly, which can weaken the connections between heart muscle cells. This structural weakness is a hallmark of arrhythmogenic right ventricular cardiomyopathy (ARVC), a condition where heart muscle tissue is progressively replaced by fat and fibrous tissue, potentially leading to irregular heart rhythms.
Research and Clinical Associations
Research has established a strong association between pathogenic variants in the PKP2 gene and ARVC. Studies indicate that mutations in this gene are found in a significant percentage of individuals diagnosed with the condition. The evidence for rs193922674 specifically highlights its role as a pathogenic factor that may act in a dominant manner, meaning only one copy of the altered gene is typically required to influence the risk. However, it is important to note that genetic penetrance—the likelihood that a person with the mutation will actually develop the disease—can be variable. Some individuals with the mutation may show clear symptoms, while others may have a much milder presentation or none at all. Clinical research continues to explore why these differences occur, including the potential influence of gender and other genetic or environmental factors.
Population Frequency
The rs193922674 variant is considered rare in the general population. Because it is not a common polymorphism, it is not typically found in large-scale population screening studies at high frequencies. Most data regarding this variant comes from clinical cohorts where individuals are being tested specifically for hereditary heart conditions. Its rarity means that the vast majority of the global population does not carry this specific mutation.
What This Information Means for You
If you have received information about this variant, it is essential to understand that genetic results are not a medical diagnosis. The presence of a pathogenic variant indicates an increased risk, but it does not guarantee that an individual will develop a heart condition. Genetic testing results should always be interpreted by a qualified healthcare professional, such as a cardiologist or a genetic counselor, who can place the findings in the context of your personal and family medical history. If you are concerned about your heart health or have a family history of cardiomyopathy, consult with your clinician to discuss appropriate screening, such as an echocardiogram or an electrocardiogram (ECG). Never make changes to your health management or medication based solely on a genetic report without professional medical guidance.
How common is this variant?
The rs193922674 variant is rare, with the G/G genotype being the most common in the general population.
Frequently asked questions
What is ARVC?
ARVC, or arrhythmogenic right ventricular cardiomyopathy, is a heart condition where the muscle of the right ventricle is replaced by fat and scar tissue. This can lead to heart rhythm problems and, in some cases, an increased risk of sudden cardiac arrest.
Does having this variant mean I have heart disease?
No, having a genetic variant does not mean you have the disease. It only indicates an increased genetic predisposition, and many people with such variants may never develop clinical symptoms.
Should I get tested for this variant?
Genetic testing is usually recommended by a doctor if there is a personal or family history of heart conditions. You should discuss the necessity of testing with a cardiologist or a genetic counselor.
Can I change my genes?
No, you cannot change your genetic code. However, knowing your genetic risks can help you and your doctor create a personalized health plan to monitor your heart and manage potential risks effectively.
Sources & further reading
Educational information only, last refreshed 9/22/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This variant is classified as pathogenic and is relevant for carrier screening in cardiac-related conditions.
This variant in the PKP2 gene is associated with arrhythmogenic right ventricular cardiomyopathy.
This variant in the PKP2 gene is associated with desmosomal proteins and is frequently observed in clinical variant databases.