MYH7 rs28937313: Understanding the Arg403Gln Variant
The genetic variant rs28937313 is a rare single nucleotide change located in the MYH7 gene, resulting in an amino acid substitution from arginine to glutamine at position 403 (p.Arg403Gln). It is one of the classic, well-documented missense mutations historically associated with familial hypertrophic cardiomyopathy (HCM). While carrier status confers a predisposition to cardiac muscle thickening, actual clinical symptoms and severity can vary widely among individuals.
What each genotype means
Typical MYH7 genetic profile
This genotype represents the common, non-variant sequence at this position in the MYH7 gene. It is not associated with the specific pathogenic risk described for the Arg403Gln mutation.
This is the most common genotype found in the general population.
Increased hypertrophic cardiomyopathy risk
This genotype includes one copy of the pathogenic Arg403Gln mutation, which is strongly associated with familial hypertrophic cardiomyopathy. This variant is known for high penetrance, meaning individuals who carry it are at a significantly increased risk of developing heart muscle thickening, though the clinical severity can vary between individuals.
This genotype is extremely rare in the general population, occurring in fewer than 1 in 10,000 individuals.
High risk hypertrophic cardiomyopathy
This genotype indicates the presence of two copies of the Arg403Gln mutation. While this specific homozygous state is exceptionally rare, it is associated with a high risk for severe hypertrophic cardiomyopathy and requires clinical evaluation by a cardiologist.
This genotype is exceedingly rare and has not been widely documented in general population databases.
What Is rs28937313 and Where Is It Located?
The single nucleotide polymorphism (SNP) rs28937313 is a specific genetic variation located on human chromosome 14 inside the MYH7 gene. At the molecular level, this variation represents a nucleotide substitution (c.1208G>A), which changes the codon for amino acid 403 from arginine to glutamine (p.Arg403Gln). The alteration occurs directly within the functional motor head domain of the beta-myosin heavy chain protein. Because this protein segment is directly involved in generating mechanical force within cardiac muscle cells, amino acid substitutions at this site can alter the mechanics of contraction and relaxation. Databases such as ClinVar and dbSNP catalog this variant as a critical reference point in cardiac genetics. The mutation is usually inherited in an autosomal dominant manner, meaning a single altered copy of the gene can be sufficient to confer an increased risk of heart disease.
The Biological Function of the MYH7 Gene
The MYH7 gene encodes the cardiac beta-myosin heavy chain, a primary component of the thick filaments within the sarcomere. Sarcomeres serve as the foundational mechanical units responsible for muscle contraction throughout the human heart ventricles and certain slow-twitch skeletal muscle fibers, as outlined in resources like MedlinePlus Genetics. During cardiac contraction, myosin heads bind to actin filaments and harness energy from adenosine triphosphate (ATP) to pull the filaments, enabling the heart muscle to pump blood efficiently. Disruptions in the MYH7 coding sequence can perturb this biomechanical cycle, either causing hypercontractility, reduced mechanical efficiency, or altered cross-bridge kinetics. Over time, these cellular-level changes can trigger secondary remodeling responses, causing the muscular walls of the heart to grow abnormally thick and stiff, a hallmark characteristic of hypertrophic cardiomyopathy.
Scientific Evidence and Clinical Association
In medical genetics literature and clinical databases such as ClinVar, the p.Arg403Gln alteration is recognized as one of the earliest identified and most extensively studied pathogenic variants associated with familial hypertrophic cardiomyopathy type 1 (CMH1). Research across diverse cohorts indicates that carriers have a heightened risk of developing left ventricular hypertrophy, left ventricular outflow tract obstruction, arrhythmias, and heart failure. However, clinical expressivity is heterogeneous: while some carriers develop significant cardiac thickening early in life or require interventions such as septal myectomy or implantable defibrillators, other individuals within the same family may exhibit a mild phenotype or late-onset symptoms. This variable expressivity suggests that secondary modifier genes, lifestyle elements, and environmental conditions modulate how strongly the variant affects cardiac architecture.
How Common Is rs28937313 Across Populations?
According to population genomics datasets such as gnomAD, rs28937313 is exceedingly rare in the general worldwide population, with an allele frequency far below 0.0001 (less than 0.01%). It is virtually absent from large cohorts of healthy individuals, consistent with its characterization as a potent, disease-associated allele under negative selection. When detected, it is predominantly identified in individuals or families undergoing targeted genetic evaluations for unexplained cardiac enlargement, sudden cardiac death histories, or familial cardiomyopathy. Because it is a recurring allele discovered across varied ancestries, clinical registries from multiple continents have reported instances of the variant, but it remains a rare finding that does not occur as common background variation in any documented ethnic group.
What to Do (and What Not to Do) With Genetic Findings
Receiving a genetic result indicating a variant like rs28937313 should never be interpreted as an automated medical diagnosis or an imminent clinical outcome. Genetics describes statistical risk, but actual cardiac structure and function must be evaluated by a medical professional using clinical diagnostics such as echocardiograms or cardiac magnetic resonance imaging (MRI). You should not alter any cardiac medications, initiate new therapies, or make drastic changes to your athletic training routines without guidance from a qualified physician. Instead, if an individual discovers they carry an MYH7 variant, the most appropriate next step is a formal consultation with a genetic counselor or a cardiologist specializing in inherited cardiovascular diseases. These professionals can confirm findings in a clinical-grade lab, assess family history, and construct an appropriate long-term monitoring strategy.
How common is this variant?
The rs28937313 variant is extremely rare in general reference populations (allele frequency <0.0001 in gnomAD), occurring almost exclusively as a recurrent, disease-associated mutation in families evaluated for cardiomyopathy.
Frequently asked questions
What is MYH7 rs28937313?
rs28937313 is a rare genetic variant in the MYH7 gene that changes the amino acid arginine to glutamine at position 403 of the beta-myosin heavy chain protein. It is widely recognized in scientific literature as a classic causative variant for familial hypertrophic cardiomyopathy.
Does having the rs28937313 variant guarantee I will develop heart disease?
No. While the variant carries high penetrance, meaning a large percentage of carriers eventually develop some physical signs of hypertrophic cardiomyopathy, the disease exhibits variable expressivity. Some carriers experience severe symptoms, while others show mild heart changes or remain asymptomatic until later in life.
How is the rs28937313 variant typically inherited?
This variant is inherited in an autosomal dominant pattern. This means an individual only needs to inherit one copy of the variant from one parent to carry the predisposition, and they have a 50% chance of passing it to each child.
What steps should I take if a consumer test reports this variant?
Consumer-grade microarray tests can have false positives on rare variants. The appropriate course of action is to review the result with a healthcare professional or genetic counselor, who can arrange confirmatory clinical testing and order cardiovascular imaging if necessary.
Sources & further reading
Educational information only, last refreshed 9/6/2026. 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.
A well-characterized pathogenic missense substitution (p.Arg403Gln) causing familial hypertrophic cardiomyopathy with elevated risk of arrhythmia and sudden cardiac death.
This coding variant in MYH7 is cataloged in ClinVar and curated for its association with genetic predisposition to familial hypertrophic cardiomyopathy.