MYOC rs74315354: Understanding the p.Gln368Ter Variant
The rs74315354 variant in the MYOC gene, often referred to as p.Gln368Ter, is a well-studied genetic marker associated with an increased risk of primary open-angle glaucoma. It functions by causing the production of a truncated myocilin protein, which is thought to accumulate in the eye's drainage tissues.
What each genotype means
Typical MYOC profile
This genotype represents the most common form of the MYOC gene, which does not include the specific p.Gln368Ter variant. Individuals with this genotype do not carry this known genetic risk factor for primary open-angle glaucoma associated with this specific variant.
This is the most common genotype found in the general population across all ancestries.
Increased glaucoma risk
This genotype indicates the presence of the p.Gln368Ter variant, which is associated with an increased risk for primary open-angle glaucoma and certain related subtypes like exfoliation glaucoma. Research suggests that this variant may lead to the accumulation of misfolded myocilin protein in the eye, potentially increasing intraocular pressure; however, penetrance is incomplete, meaning not everyone with this genotype will develop the condition. Please discuss your eye health and any necessary monitoring with an ophthalmologist.
This genotype is rare, with a global minor allele frequency of approximately 0.16%, though it is more common in European populations where it may be found in roughly 0.2% to 0.3% of individuals.
Rare variant homozygous
This genotype indicates that both copies of the MYOC gene carry the p.Gln368Ter variant. While the heterozygous state (CT) is well-documented as a risk factor for glaucoma, the clinical implications of being homozygous for this specific variant are less frequently described in scientific literature. You should consult with a genetic counselor or an ophthalmologist to discuss the implications of this rare genotype for your long-term eye health.
This genotype is extremely rare and is not typically observed in standard population frequency datasets.
What is the rs74315354 Variant?
The rs74315354 variant is a specific change in the DNA sequence of the MYOC gene, located on chromosome 1. In scientific literature, this variant is frequently identified as p.Gln368Ter, which indicates that a glutamine amino acid at position 368 is replaced by a premature stop signal. This change results in a truncated, or shortened, version of the myocilin protein. Because this variant alters the protein's structure, it is classified as a missense or nonsense mutation depending on the specific nomenclature used. It is one of the most commonly studied variants in the MYOC gene, particularly among populations of European ancestry. Researchers track this variant to understand how specific genetic changes contribute to the development of eye conditions, specifically those involving the drainage of fluid from the eye.
The Role of the MYOC Gene
The MYOC gene provides instructions for making a protein called myocilin. This protein is expressed in several parts of the eye, most notably in the trabecular meshwork, which is the tissue responsible for draining aqueous humor—the fluid that maintains pressure within the eye. When the MYOC gene functions normally, myocilin helps maintain the structural integrity and proper function of this drainage system. However, when mutations like p.Gln368Ter occur, the resulting truncated protein is prone to misfolding. This misfolded protein can accumulate within the cells of the trabecular meshwork, potentially causing cellular stress or dysfunction. This accumulation is believed to impede the outflow of aqueous humor, which can lead to elevated intraocular pressure, a primary risk factor for the development of primary open-angle glaucoma.
Research and Clinical Associations
Research has consistently associated the rs74315354 variant with an increased risk of primary open-angle glaucoma (POAG). Studies, including those using large datasets like the UK Biobank, have estimated that approximately 1 in 4 individuals carrying this variant may show evidence of glaucoma. This penetrance is considered significant, though it is important to note that not every individual with the variant will develop the disease. The risk is often described as having a high effect size for advanced glaucoma. Furthermore, recent research suggests that an individual's overall polygenic risk score for glaucoma can influence the severity and likelihood of disease manifestation in carriers of this specific MYOC variant. While the association is strong, the condition is complex, and environmental factors and other genetic modifiers likely play a role in whether an individual develops clinical symptoms.
Population Frequency
The rs74315354 variant is relatively rare in the general global population, with a minor allele frequency (MAF) of approximately 0.0016 in large databases like gnomAD. However, its frequency varies by ancestry, with the highest prevalence observed in European populations, where it typically ranges between 0.2% and 0.3%. Because it is a rare variant, it is not found in the majority of the population. Its presence is most frequently documented in clinical studies focusing on inherited eye diseases or large-scale population health cohorts. Due to its low frequency, it is not considered a common polymorphism, but rather a rare variant that carries significant clinical weight for those who inherit it.
Managing Genetic Information
Understanding your genetic status regarding the rs74315354 variant can provide insight into your personal risk profile for glaucoma, but it is not a diagnostic tool on its own. If you are aware that you carry this variant, it is essential to discuss this information with an ophthalmologist or a genetic counselor. They can provide context based on your family history and clinical eye examinations. Because glaucoma is often asymptomatic in its early stages, regular eye screenings are the most effective way to monitor eye health, regardless of your genetic status. You should never use genetic information to make medical decisions, such as starting or stopping treatments, without consulting a healthcare professional. Genetic testing results should always be interpreted within the context of a comprehensive clinical evaluation.
How common is this variant?
The rs74315354 variant is rare globally, with a minor allele frequency of approximately 0.0016, though it reaches frequencies of 0.2-0.3% in European populations.
Frequently asked questions
Does having the MYOC p.Gln368Ter variant mean I will get glaucoma?
No, having the variant does not guarantee you will develop glaucoma. Research indicates that while the variant increases risk, the penetrance is not 100%, meaning many carriers do not develop the disease.
What should I do if I know I have this variant?
If you are aware you carry this variant, you should schedule regular comprehensive eye exams with an ophthalmologist. Discuss your genetic results with your doctor so they can provide appropriate monitoring based on your individual risk.
Is this the only gene associated with glaucoma?
No, glaucoma is a complex, heterogeneous disease. While MYOC mutations are a well-known cause, many other genes and environmental factors contribute to the risk of developing the condition.
Can I be tested for this variant?
Yes, this variant can be identified through genetic testing. However, such testing should be performed in a clinical setting where you can receive professional counseling regarding the results.
Sources & further reading
Educational information only, last refreshed 9/17/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Encodes the classical Gln368STOP mutation in myocilin, a well-validated genetic cause of juvenile- and adult-onset primary open-angle glaucoma.
A major missense variant in the myocilin olfactomedin domain causative of juvenile- and adult-onset primary open-angle glaucoma.
Missense mutation in MYOC (p.Gln368Glu) predisposing carriers to elevated intraocular pressure and adult-onset primary open-angle glaucoma.
A pathogenic point mutation in MYOC strongly linked to autosomal dominant primary open-angle glaucoma with high intraocular pressure.
A pathogenic missense variant in myocilin causing trabecular meshwork disruption and juvenile-onset open-angle glaucoma.
Known as the Gln368STOP mutation in MYOC, this nonsense variant is a well-established cause of autosomal dominant juvenile- and adult-onset primary open-angle glaucoma.