Common variants move the heart's recovery time by a millisecond or two — nothing on their own. They start to matter when a medicine pushes in the same direction, which several hundred medicines do.
The QT interval is the time it takes the lower chambers of the heart to reset between beats. It is measured on an ECG, in milliseconds, and it varies between healthy people for ordinary reasons — sex, age, heart rate, potassium levels. Longer is not automatically dangerous. Much longer, or longer in the wrong circumstances, can be.
This page is worth reading carefully, because the same gene names appear here in two roles that get confused constantly.
Rare coding changes in KCNH2 and KCNJ2 cause congenital long QT syndrome — an inherited disease diagnosed with an ECG and a family history, which carries a real risk of dangerous rhythms and is managed by cardiologists. That is not what this page is about, and no variant listed here indicates it.
Common variants in and around those same genes — the four below — shift the QT interval by roughly one to three milliseconds each. On a measurement that normally runs around 400 milliseconds, that is small enough to be invisible in any individual. Nobody has ever been diagnosed with anything because of one.
Several hundred medicines prolong the QT interval as a side effect — some antiarrhythmics, some antipsychotics, some antibiotics, some antiemetics. In most people that is absorbed without consequence, because the heart has what cardiologists call repolarisation reserve: spare capacity to reset on time even when one mechanism is impaired.
Common variants like these appear to eat into that reserve. A risk score built from common QT variants was associated with drug-induced QT prolongation and with torsade de pointes, the dangerous rhythm that long QT can produce (Strauss et al., Circulation 2017). So the finding is not "this variant is bad" but something more precise and more useful: a millisecond that means nothing by itself can mean something when a drug is pushing in the same direction.
What follows from that in practice is nothing you should do alone. It is a reason the QT-prolonging medicines page exists, and a reason that potassium, other medicines and kidney function matter more to your prescriber than any of this.
Nothing, on its own. No guideline uses common QT variants to choose or avoid a drug, and none of these results is a reason to stop or refuse a prescription. If you have fainted unexplainably, if sudden cardiac death runs in your family, or if you have been told your ECG shows a long QT, those are reasons to see a doctor — and they are reasons regardless of what any variant here says.
The measurement. The QT interval spans ventricular depolarisation and repolarisation on the surface ECG and is rate-dependent, so it is reported corrected (QTc), most often by Bazett or Fridericia. Normal ranges differ by sex; thresholds commonly cited for concern are above roughly 450 ms in men and 460 ms in women, with risk rising materially above 500 ms. Correction formula, lead selection and measurement technique all introduce variation, which is why a single automated reading is not treated as definitive.
Common versus rare variation at the same loci. Loss-of-function coding variants in KCNH2 (LQT2) and KCNJ2 (Andersen-Tawil syndrome, sometimes classified LQT7) cause congenital long QT syndrome, with substantially prolonged QTc and a documented arrhythmic risk. The variants on this page are common non-coding or synonymous positions at or near those loci with per-allele effects of 1-3 ms. They are not diagnostic of, nor screening tests for, the congenital syndromes, and a page describing them should say so explicitly because the gene names invite the confusion.
Effect sizes. From the GWAS Catalog: rs12029454 (NOS1AP) 2.98 ms per allele, p = 3 x 10-45, risk allele frequency 0.15; rs10919071 (ATP1B1) 1.37 ms, p = 3 x 10-30, frequency 0.115, with a separate report of 2.05 ms (p = 1 x 10-15) for the alternate allele at frequency 0.87; rs2968863 (KCNH2) 1.35 ms, p = 2 x 10-15, frequency 0.29; rs17779747 (KCNJ2) 1.08 ms, p = 3 x 10-37, frequency 0.304. NOS1AP is the most consistently replicated common QT locus and has additionally been associated with drug-induced QT prolongation and with ventricular arrhythmia in separate work.
Repolarisation reserve and drug-induced long QT. Drug-induced QT prolongation is understood as unmasking of reduced repolarisation reserve: individuals with subclinical impairment tolerate normal conditions and decompensate under pharmacological challenge. Strauss et al. (Circulation 2017) reported that a risk score constructed from common QT-associated variants was associated with both drug-induced QT prolongation and torsade de pointes risk. This is population-level evidence for a mechanism, not a validated clinical test; no professional society recommends genotyping common QT variants before prescribing, and the established risk factors — hypokalaemia, hypomagnesaemia, bradycardia, renal impairment, female sex, concomitant QT-prolonging drugs and drug interactions affecting clearance — remain the ones clinicians act on.
Clinical status. None of these variants has diagnostic, screening or prescribing use. CredibleMeds maintains the reference classification of QT-prolonging medicines; that list, and the patient's electrolytes and other drugs, are what prescribing decisions rest on.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about QT Interval and Drug-Induced Long QT comes down to these specific, well-studied positions — not a diagnosis.
Research-derived gene–drug associations only — not a prescription, dosing guide, or medical advice. Always follow your prescriber's guidance.
| Gene | Drug | What the research shows |
|---|---|---|
| NOS1AP | QT-prolonging medicines (certain antiarrhythmics, antipsychotics, antibiotics and antiemetics) | A mechanism with population evidence behind it and no clinical test in front of it. Several hundred medicines prolong the QT interval, and most people absorb that without consequence because the heart has spare capacity to repolarise on time. Common QT variants appear to reduce that spare capacity: a risk score built from them was associated with drug-induced QT prolongation and with torsade de pointes (Strauss et al., Circulation 2017). No society recommends genotyping before prescribing, and the factors clinicians actually act on — potassium and magnesium levels, heart rate, kidney function, other QT-prolonging drugs — matter more. Useful as an explanation of why the same drug is uneventful in most people and not in everyone. (Strauss DG et al., Common Genetic Variant Risk Score Is Associated With Drug-Induced QT Prolongation and Torsade de Pointes Risk. Circulation 2017; CredibleMeds QT drug lists) |
No, and the gene names make this confusing, so it is worth being blunt. Congenital long QT syndrome is caused by rare coding changes and is diagnosed with an ECG and a family history. The variants here are common positions near the same genes that move the measurement by one to three milliseconds out of about four hundred. They are not a screening test for the syndrome and cannot rule it in or out.
Because it stops being nothing in company. Several hundred medicines prolong the QT interval, and the heart tolerates that by having spare capacity to reset on time. Common variants appear to reduce that spare capacity, which is why a score built from them tracks who gets into trouble on a QT-prolonging drug and who does not.
No. No guideline uses these variants to choose or avoid a medicine, and stopping a prescription on the basis of one would be a real risk taken to avoid a theoretical one. What your prescriber weighs — your potassium and magnesium, your heart rate, your kidney function, your other medicines — matters more and is measurable today.
If you have fainted without explanation, if sudden cardiac death has happened in your family, or if someone has told you your ECG shows a long QT. Each of those is a reason on its own, whatever any variant says.
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