MYH7 rs121913624: Understanding the p.Arg403Gln Variant
The MYH7 p.Arg403Gln variant is a well-characterized genetic change associated with familial hypertrophic cardiomyopathy. It involves a specific substitution in the beta-myosin heavy chain protein, which plays a critical role in heart muscle contraction.
What each genotype means
Typical cardiac risk
You carry two copies of the standard reference allele at this position in the MYH7 gene. This genotype is not associated with the severe familial form of hypertrophic cardiomyopathy linked to the p.Arg403Gln variant. Your baseline risk for inherited cardiac thickening from this specific marker remains typical of the general population.
Carried by virtually 100% of individuals across all global populations.
Elevated cardiomyopathy risk
You carry one copy of the pathogenic missense variant corresponding to p.Arg403Gln in MYH7, which is historically associated with familial hypertrophic cardiomyopathy inherited in an autosomal dominant pattern. Research cohorts indicate this change is strongly linked to progressive thickening of heart muscle walls and an elevated risk of ventricular arrhythmias. Because clinical penetrance and symptoms vary, clinical genetic counseling and comprehensive cardiology evaluations are recommended in medical literature for carrier families.
Extremely rare, observed in fewer than 1 in 100,000 individuals in large reference cohorts like gnomAD.
High-risk homozygous carrier
You carry two copies of the pathogenic alternative allele for this MYH7 variant. Homozygous inheritance for dominant severe cardiomyopathy variants is exceptionally documented and typically associated with severe, early-onset cardiac dysfunction in published medical genetics case reports. Comprehensive clinical evaluation and genetic counseling are standard recommendations for individuals with biallelic variants in sarcomeric genes.
Exceedingly rare and virtually absent in general reference population databases.
What is the MYH7 p.Arg403Gln Variant?
The variant known as p.Arg403Gln (often identified by the clinical identifier rs121913624) is a single nucleotide change in the MYH7 gene. Specifically, it involves a G to A substitution at nucleotide position 1208, which results in the replacement of the amino acid arginine with glutamine at position 403 of the protein. This variant is located in the head region of the beta-myosin heavy chain, a critical area for the protein's interaction with actin during muscle contraction. Because this region is highly conserved across species, changes here are often significant. This specific mutation has been extensively documented in medical literature as a pathogenic variant, meaning it is strongly linked to the development of specific heart conditions. It is considered a classic example of a sarcomeric mutation that alters the mechanical function of the heart's contractile machinery.
The Role of the MYH7 Gene
The MYH7 gene provides instructions for making a protein called beta-myosin heavy chain. This protein is a primary component of the sarcomere, the basic unit of muscle contraction in the heart. Within the heart muscle, beta-myosin heavy chain works alongside other proteins to generate the force necessary for the heart to pump blood throughout the body. When the MYH7 gene functions normally, it ensures that heart muscle fibers contract and relax with the appropriate timing and strength. Mutations in this gene can disrupt the structure or function of the myosin protein, leading to inefficient contraction or structural changes in the heart muscle. Such disruptions are a common cause of inherited cardiomyopathies, which are diseases of the heart muscle that can affect its ability to pump blood effectively.
Research and Clinical Associations
The p.Arg403Gln variant is strongly associated with familial hypertrophic cardiomyopathy (HCM), a condition characterized by the thickening of the heart muscle. Research has consistently shown that this variant segregates with the disease in affected families, meaning individuals who inherit the variant are significantly more likely to exhibit signs of HCM. Clinical studies have reported this variant in numerous individuals with the condition, and functional laboratory studies using animal models have confirmed that it disrupts normal myosin function, leading to a phenotype consistent with HCM. Because of this robust body of evidence, including segregation data and functional analysis, expert panels have classified this variant as pathogenic. It is important to note that while the association with HCM is strong, the clinical expression of the disease can vary between individuals, even those within the same family.
Population Frequency and Prevalence
The p.Arg403Gln variant is extremely rare in the general population. Large-scale genomic databases, such as gnomAD, typically show that this variant is absent or found at an exceptionally low frequency in individuals without diagnosed heart conditions. This rarity in the general population supports its classification as a pathogenic variant, as it is not a common polymorphism found in healthy individuals. Because it is so rare, it is not typically included in standard, broad-spectrum genetic screening panels unless there is a specific clinical suspicion of inherited cardiomyopathy. Its presence is almost exclusively identified in the context of clinical genetic testing for patients who have already been diagnosed with or have a strong family history of hypertrophic cardiomyopathy.
Navigating Genetic Information
Understanding a genetic variant like p.Arg403Gln requires careful interpretation by qualified healthcare professionals, such as genetic counselors or cardiologists. If you or a family member have been identified as carrying this variant, it is essential to discuss the findings with a medical specialist who can provide context based on your personal and family health history. Genetic information is complex, and the presence of a variant does not always guarantee that a specific health outcome will occur, nor does it provide a complete picture of an individual's overall risk. You cannot use this information to self-diagnose or make independent medical decisions. Always consult with your clinician to understand what this result means for your health, what screening or monitoring might be appropriate, and how it may impact other family members.
How common is this variant?
The p.Arg403Gln variant is extremely rare in general populations, with a frequency of less than 0.00001 in databases like gnomAD.
Frequently asked questions
What is the link between MYH7 and hypertrophic cardiomyopathy?
The MYH7 gene encodes a protein essential for heart muscle contraction. Mutations in this gene, including p.Arg403Gln, can cause the heart muscle to thicken abnormally, which is the hallmark of hypertrophic cardiomyopathy.
Is the p.Arg403Gln variant always inherited?
Yes, this variant is typically inherited in an autosomal dominant pattern, meaning an individual only needs to inherit one copy of the variant from one parent to be at risk for the associated condition.
What should I do if I have this variant?
If you are identified as a carrier of this variant, you should consult with a cardiologist or a genetic counselor. They can help you understand your personal risk and determine if regular cardiac monitoring is necessary.
Does having this variant mean I will definitely develop heart disease?
While this variant is strongly associated with hypertrophic cardiomyopathy, the clinical expression can vary. A medical professional can help assess your specific risk based on your family history and clinical evaluations.
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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This variant is a pathogenic mutation in the MYH7 gene associated with hypertrophic cardiomyopathy.
This variant is a pathogenic mutation in the MYH7 gene associated with hypertrophic cardiomyopathy.
This variant is a pathogenic mutation in the MYH7 gene associated with hypertrophic cardiomyopathy.
This missense variant in MYH7 is associated with hypertrophic cardiomyopathy, specifically noted for its role in abnormal contractile protein function.
Sarcomeric beta-myosin heavy chain mutation p.Arg403Gln causing familial hypertrophic cardiomyopathy.
This coding variant in MYH7 is cataloged in ClinVar and curated for its association with genetic predisposition to familial hypertrophic cardiomyopathy.