CPT2 Genotype (p.Lys414ThrfsTer7)

This result reports one specific change in CPT2 that the lab's sequencing panel found. CPT2 is a gene your muscles and liver need to burn fat for energy. The change, listed on your report as c.1239_1240del or p.Lys414ThrfsTer7, removes two letters of the gene's code. That throws off how the rest of the gene is read, so the copy carrying it cannot make a working CPT2 enzyme. Labs classify it as pathogenic, meaning there is strong evidence it can cause CPT2 deficiency when a person inherits two non-working copies.

If your report shows one copy, you are a carrier. CPT2 deficiency is recessive: it needs a non-working copy from each parent, and carriers usually have no disease. One copy still matters in two practical ways. It is worth knowing if you take a statin or ever have unusual muscle pain, and it is useful information for family planning.

What CPT2 Does

When your body needs extra energy, during prolonged exercise, fasting, cold, fever or stress, it leans on fat. Long fat molecules have to be carried into the mitochondria, the parts of each cell that burn fuel, before they can be used. CPT2 is the enzyme on the inside of that doorway: it releases the fat so it can be burned. When CPT2 does not work well, muscles can run short of fuel under strain.

CPT2 deficiency comes in three forms. The muscle form is the most common and usually the mildest, and it is the most common inherited disorder of fat use affecting muscle. People with it are typically well between episodes, then get muscle pain, weakness and sometimes muscle breakdown (rhabdomyolysis) after long exercise or other strains; exercise is the main trigger, and men are more often affected than women. Two rarer forms start in newborns or infants and are severe, affecting the liver, heart and brain.

What This Variant Does

Your CPT2 enzyme is normally a chain of 658 building blocks. This deletion changes the chain at position 414 and ends it at position 420, so the enzyme is cut off well before its normal end. Geneticists call this a frameshift. Older papers describe the same deletion under other names, such as Q413fs or c.1238_1239delAG, because the two deleted letters sit in a repeat and can be numbered either way.

ClinVar, the US public database of variant classifications, lists it as pathogenic or likely pathogenic, with multiple labs agreeing and no conflicts. In two reported families, children or fetuses with two copies had the severe early forms of CPT2 deficiency, and in one of them CPT2 activity was undetectable. That is strong evidence this copy of the gene does not work.

What Being a Carrier Means

With one copy, your other CPT2 copy keeps working. GeneReviews, a standard clinical reference, states that carriers in affected families can show partly reduced CPT2 activity on lab testing but generally have no symptoms. One family study includes a woman carrying the same deletion (reported there as Q413fs) on one copy: she had no symptoms, while two sisters who also carried a second CPT2 change had muscle attacks.

Carriers and Muscle Symptoms: What Is Known

There is a real but limited body of evidence that some carriers of a CPT2 change get muscle symptoms under heavy strain. It comes from case reports and small studies:

• Case reports: two athletes with one copy of a different CPT2 change (p.Ser113Leu) had muscle pain after strenuous exercise, one with muscle breakdown after heavy exercise and a fever. The same clinic later described a third carrier with symptoms; all three were active adults (a professional tennis player and an amateur marathon runner among them) whose attacks followed hard physical effort, such as a tennis match, a run on a hot day or an afternoon of heavy garden work.
• A small physiology study: of three carriers tested on an exercise bike, the two who had symptoms burned fat during long exercise about as poorly as people with the full condition.
• Patient series: some people with confirmed attacks have only one CPT2 change found. That may mean a second change was missed, or that some carriers do get symptoms.

What is not known: no large study has measured how often carriers get muscle symptoms, and the symptomatic carriers reported so far mostly had other CPT2 changes, not this deletion. The evidence is enough to take muscle symptoms seriously if they happen, not enough to predict that they will.

Why It Appears on a Heart and Lipid Panel

Statins are the main cholesterol-lowering medicine, and muscle complaints are one of the main reasons people stop taking them. Among statin users in general, serious statin muscle injury is rare: the American Heart Association puts it below 0.1 percent, and in blinded trials muscle aches were barely more common on a statin than on a placebo. For people who need a statin, the benefits greatly outweigh the risks.

A small number of people have an underlying muscle condition that a statin can bring to the surface, and CPT2 is one of the genes involved. In a study of 136 people who had muscle problems on cholesterol-lowering drugs, carriers of CPT2 deficiency were about 13 times more common than expected in the general population. That is an association from one cross-sectional study, not proof that carriers will react to statins, and it cannot tell you your own chance of a problem; the rate of serious statin muscle injury in CPT2 carriers has not been measured. It is why your report lists this variant under statin-associated myopathy.

Where CK Testing Fits

Creatine kinase (CK) is an enzyme that leaks into the blood when muscle is damaged. Clinicians check it when someone has muscle symptoms, especially on a statin, and read it against the lab's upper limit of normal alongside the symptoms. Small rises are common after exercise. Very high levels with muscle pain point to real muscle injury.

Two points matter for CPT2. In people with CPT2 deficiency, CK is usually normal between episodes, so a normal routine CK does not rule out a problem during a strain. And a CK result is most useful when you have symptoms.

Before someone starts a statin, the 2013 American College of Cardiology and American Heart Association cholesterol guideline considered a baseline CK reasonable for people at higher risk of muscle problems, such as a personal or family history of muscle disease or statin intolerance, or medicines that raise the risk. It has since been replaced by the 2018 American Heart Association and American College of Cardiology guideline, which advises a CK test if muscle symptoms are severe or there is weakness, and advises against routine CK checks. So your clinician may choose to check one before a statin for later comparison; whether and when is their call.

Two Copies

Two copies (del/del) would mean both CPT2 copies are non-working, which is CPT2 deficiency. In two reported families with two copies of this deletion, the children or fetuses had the severe early form, found before birth. Because the deletion is rare, having two copies is very rare; none were seen among gnomAD's more than 800,000 people, which is what chance alone would predict. Because the reported cases were so severe, a del/del result should first be confirmed, and your lab's report recommends verifying reported variants. Review it promptly with a clinician and a genetics team.

How Common It Is

Outside Ashkenazi Jewish ancestry this deletion is very rare (about 1 in 28,000 people of non-Finnish European ancestry in gnomAD, and not seen in any other named ancestry group); across all of gnomAD it is about 1 in 4,000. It is much more common in people of Ashkenazi Jewish ancestry, where about 1 in 97 people carries one copy. In an early study, everyone found with it was of Ashkenazi Jewish ancestry, which points to a shared founder.

How Results Are Reported

Your report shows your two copies of this spot in the gene, one from each parent. A dash (-) means the usual sequence, and "del" means the two-letter deletion. CPT2 is read on the forward strand of chromosome 1, so the report and the scientific name describe the same thing.

What this means for you: for most people this result is either clear or a carrier result. Neither is a diagnosis.

Do You Need to Repeat This Test?

Your DNA does not change, so you do not need to repeat this test to track changes. Your clinician or a genetic counselor may order a confirmation test, for example before family-planning decisions; your lab's report also recommends confirming reported variants.

What to Do With Your Result

If you carry one copy, these are reasonable steps to discuss with your clinician:

• Tell your prescribers: add this result to your medical record, so whoever prescribes a statin knows about it.
• Report muscle symptoms on a statin: unexplained muscle pain, weakness or dark, cola-colored urine should be reported promptly, and your clinician may check your CK.
• Do not stop a prescribed statin on your own: whether you need a statin depends on your heart risk, and your prescriber can take this result into account.
• Notice severe exercise-related pain: severe muscle pain or dark urine after long, hard exercise or a long fast is worth a medical review.
• Use it for family planning: if you are planning a pregnancy, genetic counseling can arrange carrier testing for your partner. If both partners carry a non-working CPT2 copy, each pregnancy has a 25 percent chance of CPT2 deficiency.
• Tell blood relatives: your parents, brothers and sisters may also carry it. Your lab's report recommends testing biological family members, and genetic counseling can advise on testing relatives.

For most carriers, this is a quiet result: useful to have on record, not a reason for worry.