MMACHC rs398124292: What Your Genotype Means
The rs398124292 variant is a specific genetic change located within the MMACHC gene. It is associated with methylmalonic aciduria and homocystinuria, cblC type, a rare metabolic disorder that affects how the body processes vitamin B12.
What each genotype means
Carrier of variant
This genotype indicates you are a carrier of the c.271dupA variant, also known as p.R91Kfs*14. While carriers are typically asymptomatic, this variant is associated with autosomal recessive methylmalonic aciduria and homocystinuria, cblC type, and you should consult a genetics professional regarding family planning or clinical concerns.
This genotype is rare in the general population.
Associated with cblC type
This genotype indicates the presence of two copies of the c.271dupA variant, which is a well-established pathogenic mutation. This is associated with methylmalonic aciduria and homocystinuria, cblC type, a condition that can cause developmental, neurological, and vision-related health issues; clinical correlation and consultation with a medical geneticist are essential.
This genotype is very rare and is associated with a known clinical disorder.
Understanding the Variant and Its Location
The variant rs398124292 is a genetic alteration found within the MMACHC gene, which is located on chromosome 1 at position 45,507,545. In genetic literature, this specific variant is often referred to as c.271dupA. This notation indicates that an extra adenine (A) nucleotide has been inserted into the DNA sequence at a specific point. This type of change is known as a frameshift mutation, which can significantly alter the way the cell reads the genetic instructions to build a protein. Because the MMACHC gene provides the blueprint for a critical enzyme, changes like this can disrupt the normal production or function of that protein, potentially leading to downstream health effects related to metabolic processes.
The Role of the MMACHC Gene
The MMACHC gene is responsible for producing an enzyme that plays a vital role in the metabolism of vitamin B12, also known as cobalamin. Vitamin B12 is an essential nutrient that the body must process into specific cofactors, namely adenosylcobalamin and methylcobalamin, to function correctly. These cofactors are necessary for the body to break down certain proteins and fats and to maintain healthy neurological and blood functions. When the MMACHC gene is altered, the resulting enzyme may be non-functional or absent. This deficiency prevents the body from properly processing vitamin B12, leading to the accumulation of toxic substances like homocysteine and methylmalonic acid, which can cause significant health challenges if left unmanaged.
Research and Clinical Associations
Scientific research has established a strong link between variants in the MMACHC gene and a condition known as methylmalonic aciduria and homocystinuria, cblC type. This is an autosomal recessive disorder, meaning an individual typically needs to inherit two copies of a pathogenic variant—one from each parent—to manifest the condition. Clinical studies have documented that individuals with this condition may experience developmental delays, neurological issues, blood abnormalities, and vision problems such as optic atrophy. The evidence for the pathogenicity of variants like c.271dupA is considered high in clinical settings, as they are frequently identified in patients diagnosed with this metabolic disorder. Genetic testing and clinical correlation are essential for understanding the specific impact of these variants on an individual's health.
What You Can Do With This Information
If you have received information about this variant, it is important to understand that genetic data should always be interpreted by a qualified healthcare professional, such as a genetic counselor or a medical geneticist. This variant is associated with a rare, serious metabolic condition, and its presence does not automatically imply a diagnosis. A clinician can help place this information in the context of your personal health history, family history, and other diagnostic tests. If you are concerned about your results or potential health risks, do not attempt to self-diagnose. Instead, schedule an appointment with a medical professional who can provide appropriate guidance, discuss the necessity of further testing, and explain the implications for you and your family members.
How common is this variant?
The rs398124292 variant is considered rare in the general population. It is most frequently identified in clinical settings among individuals undergoing diagnostic testing for metabolic disorders.
Frequently asked questions
What is the cblC type of methylmalonic aciduria?
It is a rare, inherited metabolic disorder caused by a deficiency in the MMACHC enzyme. This deficiency impairs the body's ability to process vitamin B12, leading to the buildup of harmful compounds.
Is rs398124292 the same as c.271dupA?
Yes, in the context of the MMACHC gene, rs398124292 is the identifier used to refer to the c.271dupA mutation. Both terms describe the same specific genetic change.
Can I be a carrier of this variant?
Yes, it is possible to be a carrier if you have one copy of the variant. Carriers typically do not show symptoms of the condition because they have one functional copy of the gene.
Should I be worried if I have this variant?
Genetic variants should be discussed with a healthcare provider or genetic counselor. They can help you understand what the result means for your health and whether any follow-up testing is necessary.
Sources & further reading
Educational information only, last refreshed 9/18/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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