KCNQ1 rs63750083: Understanding the p.Arg518Ter Variant
The rs63750083 variant in the KCNQ1 gene is a rare genetic alteration that introduces a premature stop signal in the protein sequence. This variant is associated with an increased predisposition to congenital Long QT Syndrome type 1, a condition that can affect the heart's electrical rhythm.
What each genotype means
Typical KCNQ1 genotype
This is the most common genotype, representing the absence of the specific p.Arg518Ter truncation variant. Individuals with this genotype do not carry this specific genetic risk factor for Long QT Syndrome type 1 associated with this variant.
This is the wild-type genotype found in the vast majority of the human population.
Increased arrhythmia risk
This genotype indicates the presence of one copy of the p.Arg518Ter variant, which creates a premature stop signal in the KCNQ1 protein. Research suggests this type of truncation can lead to loss-of-function in potassium channels, which is strongly associated with an increased predisposition to Long QT Syndrome type 1 and potential cardiac arrhythmias. Please discuss these findings with a cardiologist or genetic counselor to understand your personal health context.
This genotype is extremely rare, occurring in fewer than 1 in 20,000 individuals based on current gnomAD data.
High risk profile
This genotype indicates the presence of two copies of the p.Arg518Ter variant. Because this variant causes a premature truncation of the KCNQ1 protein, carrying two copies is expected to significantly impact the function of cardiac potassium channels and substantially increase the risk of Long QT Syndrome type 1. It is essential to consult with a medical professional or cardiac specialist regarding this result.
This genotype is exceptionally rare and has not been observed at significant frequencies in large-scale population databases.
What is the rs63750083 Variant?
The rs63750083 variant, also identified as c.1552C>T or p.Arg518Ter, is a specific change in the DNA sequence of the KCNQ1 gene. Located in exon 12, this variant involves a single nucleotide substitution that creates a premature translation stop signal. In genetic terms, this is known as a nonsense mutation. Instead of producing a full-length, functional protein, the cellular machinery stops reading the genetic code early, resulting in a truncated or shortened version of the KCNQ1 protein. Because the protein is incomplete, it often fails to perform its intended role within the cell. This type of variant is significant in clinical genetics because it typically leads to a loss-of-function effect, where the body lacks a sufficient amount of the normal, working protein required for specific physiological processes.
The Role of the KCNQ1 Gene
The KCNQ1 gene provides instructions for making a protein called Kv7.1, which acts as a potassium channel. These channels are essential for the normal function of cardiac muscle cells. They allow positively charged potassium ions to flow out of cells, a process that is critical for the repolarization phase of the heart's electrical cycle. This phase allows the heart muscle to reset and prepare for the next beat. When KCNQ1 channels function correctly, they ensure that the heart's electrical activity, measured as the QT interval on an electrocardiogram (ECG), remains within a normal range. Disruptions to this gene can interfere with the heart's ability to reset its electrical charge, potentially leading to prolonged intervals between heartbeats, which is the hallmark of Long QT Syndrome.
Research and Clinical Associations
Research associates variants in KCNQ1, including those that cause truncation like rs63750083, with Long QT Syndrome type 1 (LQT1). LQT1 is a hereditary condition that increases the risk of cardiac arrhythmias, which are irregular heartbeats that can sometimes be life-threatening. The evidence for KCNQ1's role in LQT1 is robust, as it is one of the primary genes linked to the condition. However, the clinical expression of these variants can be highly variable. Not every individual with a KCNQ1 variant will experience the same symptoms, and some may have a 'concealed' phenotype where their ECG readings appear normal at rest. Because this specific variant is rare, clinical data is limited compared to more common mutations. It is important to note that genetic predisposition does not guarantee the development of a clinical condition, and environmental or other genetic factors often play a role.
Population Frequency
The rs63750083 variant is classified as extremely rare in global population databases such as gnomAD, with a frequency reported at less than 0.00005. Because it is so uncommon, it is not typically found in the general population and is usually identified in clinical settings during the investigation of individuals or families with a history of unexplained cardiac events or diagnosed arrhythmias. Its rarity means that large-scale population studies have limited data on its distribution across different ancestral groups. When such rare variants are identified, they are often considered 'private' or family-specific mutations. If you have received information about this variant through genetic testing, it is essential to consult with a genetic counselor or a cardiologist who specializes in inherited cardiac conditions to understand what this means for your specific health profile.
Managing Genetic Information
Genetic information regarding variants like rs63750083 should be interpreted within the context of a comprehensive clinical evaluation. If you or a family member have been identified as a carrier of this variant, you should discuss the findings with a healthcare professional, such as a cardiologist or a clinical geneticist. They can provide context based on your personal and family medical history, which is crucial for assessing risk. You cannot diagnose yourself or determine your health outcomes based on this information alone. Avoid making any changes to medications or lifestyle based on genetic reports without direct guidance from your doctor. A medical professional can help determine if further testing, such as an ECG or stress test, is appropriate to monitor your heart health and provide personalized guidance on managing potential risks.
How common is this variant?
The rs63750083 variant is extremely rare in the general population, with a frequency of less than 0.00005 in gnomAD.
Frequently asked questions
What is Long QT Syndrome type 1?
Long QT Syndrome type 1 (LQT1) is an inherited heart condition that affects the electrical system of the heart. It causes a delay in the heart's ability to recharge between beats, which can lead to dangerous heart rhythms.
Does having this variant mean I have heart disease?
Not necessarily. While this variant is associated with a higher risk of LQT1, genetic predisposition is only one factor. A clinical evaluation by a cardiologist is required to determine if the variant is affecting your heart health.
What should I do if I have this variant?
You should schedule an appointment with a cardiologist or a genetic counselor. They can review your medical history and determine if any diagnostic tests, such as an ECG, are necessary.
Is this variant common?
No, this variant is extremely rare. It is not found in the vast majority of the population and is typically only identified in specific clinical contexts.
Sources & further reading
Educational information only, last refreshed 9/20/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs63750083?
Upload a raw DNA file from 23andMe, AncestryDNA, MyHeritage, or FamilyTreeDNA and see this variant — plus thousands more — interpreted in your full report.
Get my report — $29Related variants in KCNQ1
A rare variant in the KCNQ1 gene associated with Long QT syndrome.
Pathogenic missense variant associated with Long QT syndrome type 1.
This variant is associated with Long QT syndrome 1, a condition affecting the heart's electrical activity.
Pathogenic variant associated with Long QT Syndrome type 1 (Romano-Ward syndrome).
Intronic variant in KCNQ1 associated with type 2 diabetes susceptibility and fasting glucose levels.
Associated with type 2 diabetes risk and regulation of pancreatic beta-cell insulin secretion.