KCNH2 rs199472695: Understanding This Rare Genetic Variant
The rs199472695 variant is a rare genetic change in the KCNH2 gene that results in a missense substitution. It is associated with Long QT syndrome type 2 (LQT2), a condition that affects the heart's electrical activity.
What each genotype means
Typical cardiac repolarization
You carry two copies of the common reference allele for this site in the KCNH2 gene. Research shows that this baseline genotype is not linked to congenital Long QT syndrome type 2 or impaired hERG potassium channel function. It represents the standard electrical repolarization pattern observed across human populations.
Carried by more than 99.99% of individuals across all major global ancestries.
Elevated Long QT risk
You carry one copy of the rare T missense variant (p.Ala614Val) located in the pore-forming domain of the KCNH2 potassium channel. Published clinical literature links heterozygous carriage of this mutation with autosomal dominant Long QT syndrome type 2 (LQT2), which can alter cardiac repolarization and increase susceptibility to ventricular arrhythmias. Because clinical penetrance can vary and evidence strength remains limited, consult a cardiologist or genetic counselor to discuss clinical evaluation.
Extremely rare across all continental populations, observed in fewer than 1 in 100,000 individuals in large reference datasets such as gnomAD.
Severe arrhythmia susceptibility
You carry two copies of the rare T variant in the KCNH2 gene. Because this missense change disrupts critical pore function in the hERG potassium channel, homozygous inheritance would be predicted to severely compromise cardiac repolarization, although homozygous individuals are essentially unobserved in reference populations. Comprehensive cardiac evaluation and consultation with a cardiovascular genetic specialist are strongly advised.
Virtually unobserved in global reference cohorts, with a frequency far below 1 in 1,000,000.
What is the rs199472695 Variant?
The rs199472695 variant is a specific change in the DNA sequence of the KCNH2 gene, technically identified as a missense substitution (c.1841C>T, p.Ala614Val). This means that at a specific position in the genetic code, a single nucleotide is replaced, leading to the substitution of one amino acid for another in the resulting protein. This variant is located within the pore-forming domain of the KCNH2 protein. The pore-forming domain is a critical region of the ion channel that allows potassium ions to pass through the cell membrane. Changes in this specific area can disrupt the normal function of the channel, which is essential for maintaining the heart's electrical rhythm.
The Role of the KCNH2 Gene
The KCNH2 gene provides instructions for making a protein that forms a potassium channel known as hERG or Kv11.1. These channels are vital for the heart's function because they help regulate the flow of potassium ions out of heart muscle cells. This flow of ions is responsible for the repolarization phase of the cardiac action potential, which allows the heart muscle to reset and prepare for the next beat. When KCNH2 channels do not function correctly, the repolarization process can be delayed, leading to a prolonged QT interval on an electrocardiogram. This electrical instability can increase the risk of abnormal heart rhythms, which is the hallmark of Long QT syndrome type 2.
Research and Clinical Associations
Scientific research has associated the p.Ala614Val substitution with Long QT syndrome type 2 (LQT2). Studies have identified this variant in individuals presenting with clinical features of LQT2, such as a prolonged corrected QT interval, which can be measured via an electrocardiogram. The evidence for this variant's pathogenicity is grounded in its location within the critical pore-forming domain and its observed impact on channel function. However, it is important to note that the clinical expression of genetic variants can vary significantly between individuals. While this variant is linked to LQT2, the presence of the variant alone does not guarantee a specific clinical outcome, and medical professionals evaluate such findings in the context of a patient's full clinical history and diagnostic testing.
Population Frequency
The rs199472695 variant is extremely rare in the general population. According to data from large-scale genomic databases like gnomAD, the minor allele frequency is typically reported as less than 0.00001 or it remains unobserved in many populations. Because it is so rare, it is not considered a common polymorphism. Its scarcity in the general population is consistent with its classification as a pathogenic variant associated with a specific, rare Mendelian disorder.
What You Can Do With This Information
If you have received information about this variant, it is essential to understand that this is not a medical diagnosis. Genetic information is complex, and the clinical significance of any variant should be interpreted by a qualified healthcare provider, such as a cardiologist or a genetic counselor. They can help place this finding in the context of your personal and family health history. If you are concerned about heart health or potential symptoms like fainting or palpitations, consult your physician. Never make changes to your medications or health regimen based on genetic reports without first discussing them with your clinician or pharmacist, as they are the only ones who can provide appropriate medical guidance.
How common is this variant?
The rs199472695 variant is extremely rare in gnomAD global populations, with a minor allele frequency of less than 0.00001 or remaining unobserved.
Frequently asked questions
What is Long QT syndrome type 2?
Long QT syndrome type 2 (LQT2) is an inherited heart condition caused by mutations in the KCNH2 gene. It affects the heart's electrical system, potentially leading to an irregular heartbeat and an increased risk of fainting or sudden cardiac events.
Does having this variant mean I have LQT2?
Not necessarily. While this variant is associated with LQT2, genetic testing results must be interpreted by a medical professional alongside clinical exams like an ECG. Only a doctor can provide a diagnosis based on your specific health profile.
Can I change my diet to fix this variant?
No, genetic variants like this are inherited and cannot be changed by diet or lifestyle. If you have concerns about your heart health, you should speak with a cardiologist about appropriate monitoring and management strategies.
Where can I find more information about KCNH2?
You can find reliable information about the KCNH2 gene and its associated conditions on resources like MedlinePlus Genetics or the NCBI Gene database. These sites provide educational summaries based on current scientific research.
Sources & further reading
Educational information only, last refreshed 10/18/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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