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RET codon and risk level: why the exact variant decides timing | CION Cancer Clinics
Not every RET fault carries the same risk. The exact position of the fault, called the codon, predicts how early medullary thyroid cancer is likely to start. Guidelines sort RET faults into highest, high and moderate risk, and that level decides when the thyroid is removed and when other checks begin. This page explains how to find your codon and what each level usually means. At CION Cancer Clinics, our oncologists explain what a gene result means for you and your family, and plan the checks that follow.
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Medically reviewed by Dr. Naresh GunduConsultant Medical Oncologist · MBBS, DNB (Internal Medicine), DM (Medical Oncology, AIIMS) · last reviewed September 2026, next review due September 2027
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On this page
- Why does the exact RET variant matter so much?
- What do highest, high and moderate risk actually mean?
- How does the codon turn into a plan for your child?
- What do the words on a RET report mean?
- Higher-risk and moderate-risk codons, compared
- What this page cannot tell you
- Four things families tell us, and what is actually true
- Common questions about RET codons and risk
The short answer
Why does the exact RET variant matter so much?
Because different RET faults behave very differently. The exact position of the fault in the gene predicts how early medullary thyroid cancer is likely to start. That, in turn, decides when the thyroid should be removed and when checks for other glands begin.
What a codon is
A gene is written in three-letter words called codons. Each codon tells the cell which building block to add next. RET faults tend to cluster at a handful of codons, and each has been studied across many families worldwide.
Why guidelines sort them into levels
Studying those families showed a clear pattern. Some codons cause thyroid cancer in infancy. Others usually cause it much later, sometimes not until adult life. Guidelines therefore group RET faults into highest, high and moderate risk, and time surgery to match.
Why this is unusual in cancer genetics
For most inherited cancer genes, the gene name alone guides the plan. RET is different. A fault at one codon can mean surgery for a baby, while a fault a short distance away can mean years of simple blood tests first. That is why the full variant name on the report matters more than the word positive.
The risk level is about timing. Every level still needs a plan.The three levels
What do highest, high and moderate risk actually mean?
These levels come from the American Thyroid Association guideline, which most specialists in India also follow.
Highest risk
One specific fault at codon 918, written M918T. It causes the syndrome called MEN2B, and thyroid cancer can begin in the first year of life.
Usually means
- Thyroid removal within the first year
- Surgery by a team used to operating on infants
High risk
Faults at codon 634, and one at codon 883. These cause MEN2A and carry an early but slightly later thyroid risk.
Usually means
- Thyroid removal by about the age of five
- Earlier if blood markers rise
Moderate risk
Every other known RET fault. Cancer tends to start later, and the pace varies more from family to family.
Usually means
- Regular checks from about the age of five
- Surgery timed by the blood markers
A variant nobody has classified yet
Rare RET changes may be of uncertain significance. They are not treated as a risk level until evidence builds. Testing other relatives with and without thyroid cancer can sometimes help the laboratory decide which way it falls.
An uncertain result should not lead to surgery on its own.Not sure whether this applies to you?
Ask an oncologistFrom result to plan
How does the codon turn into a plan for your child?
-
The report names the exact fault
It will read something like C634R or M918T. The counsellor matches that to its published risk level.
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A baseline blood test and scan
Calcitonin, a hormone made by the cells where this cancer starts, is measured. A neck ultrasound looks at the thyroid and nearby lymph nodes.
-
The surgical timing is agreed
For higher levels, a date is set in early childhood. For moderate risk, regular checks continue and surgery follows the calcitonin trend.
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Checks for other glands are scheduled
Tests for an adrenal tumour, and for overactive parathyroid glands, start from about the age of eleven for higher levels and in the mid-teens for moderate risk.
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The plan is reviewed as the child grows
Results, growth and new evidence can shift the timing. The plan should be revisited every year, not written once and filed.
On your report
What do the words on a RET report mean?
- Codon
- A three-letter word in the gene's code. The number tells you its position in the gene.
- Exon
- A section of the gene that carries instructions. RET faults cluster in a few exons.
- Variant name, such as C634R
- The normal building block, its position, and what replaced it. The same change may also appear as p.Cys634Arg.
- Germline
- Present in every cell from birth, so it can be inherited. This page is only about germline RET.
- Calcitonin
- A hormone from the thyroid's C-cells. A rising level is the earliest sign that cancer may be forming.
- Phaeochromocytoma
- A tumour of the adrenal gland that releases stress hormones. It is part of MEN2 and is usually not cancer.
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Side by side
Higher-risk and moderate-risk codons, compared
Highest or high risk
Moderate risk
Thyroid cancer can start in infancy or early childhood
Thyroid cancer usually starts later
Surgery is planned by age, before calcitonin rises
Surgery is timed by the calcitonin trend
Adrenal checks begin in late childhood
Adrenal checks begin in the mid-teens
Children are tested as early as possible
Children are still tested early, before checks start
Being straight with you
What this page cannot tell you
It cannot tell you what your family's specific variant means. What your specific variant means is a question for the counsellor who ordered the test. Risk levels describe groups of families. Your child's plan also depends on their calcitonin, their scan and your family's own history.
It cannot set a surgery date
The age ranges in guidelines are starting points. An experienced endocrine surgeon and paediatrician decide together, and parents are part of that decision. Evidence for some rarer codons is still thin, and studies so far are small.
Who this does not apply to
Most people with thyroid nodules or ordinary thyroid cancer do not need a RET test. This page is for families where a germline RET fault has already been found. A RET change found only in a tumour is a different matter, and is covered under targeted therapy.
Bring every report you have, including old ones from other hospitals. The exact variant name is what matters most.Commonly believed
Four things families tell us, and what is actually true
"Moderate risk means we can ignore it for now."
Moderate describes timing, not safety. Regular checks still start in early childhood, and missed checks are the main way a treatable cancer becomes a harder one.
"My father's cancer came late, so my son's will too."
The codon predicts the pattern better than one relative's story. Timing can differ between members of the same family, so each child needs their own checks.
"Removing the thyroid so young is too extreme."
For higher-risk codons, waiting risks cancer that has already spread. Early surgery aims to remove the thyroid before cancer forms, and children manage well on daily thyroid tablets.
"Once the thyroid is out, the RET problem is over."
The adrenal and parathyroid glands still carry risk. Those checks continue for life, and matter before any operation or pregnancy.
Questions we are asked
Common questions about RET codons and risk
Where on my report do I find the codon?
Look for a line naming the RET gene with a letter, a number and another letter, such as C634R. The number is the codon. The report may also give a longer version starting with p. If you cannot find it, ask the laboratory or your counsellor to point it out.
Is my child's risk level the same as mine?
If your child inherits the fault, they inherit the same codon and the same risk level. What can differ is how early cancer actually starts. That is why children are tested and followed on their own schedule rather than simply copying a parent's.
What if my variant is not on any risk list?
Some rare RET changes are too uncommon to classify firmly. The laboratory may call it a variant of uncertain significance. That is not a positive result and should not lead to surgery on its own. Classifications are reviewed as evidence grows.
Can the risk level change over time?
The codon itself never changes. What can change is how guidelines grade it, as more families are studied. A counsellor should tell you if your variant is reclassified, so keep your contact details up to date with the clinic.
Why is calcitonin checked if surgery is planned anyway?
Calcitonin tells the surgeon whether cancer may already be present. A raised level can bring surgery forward or change how much of the neck is explored. After surgery, it becomes the main test for checking that nothing has come back.
Does MEN2B look different from MEN2A?
Often, yes. Children with MEN2B may have small bumps on the lips or tongue, a tall slim build, or long-standing bowel problems. Many are the first in their family with the fault. These signs can prompt testing before any thyroid lump is felt.
Do adults found to carry RET need surgery too?
Usually yes, but the timing depends on the codon, the calcitonin level and the ultrasound. An adult may already have a small cancer, so the operation may be larger. Adrenal checks should be done before any surgery.
Is RET testing covered by Aarogyasri or insurance?
Stand-alone genetic tests are often not covered, while thyroid surgery may be. Coverage varies by scheme and policy. Ask for a written estimate before testing, and ask whether the family's known-fault test for relatives costs less than the first test.
Your Specialists
Meet CION's oncologists. Bring your family history or genetic report to them.
Our medical oncologists see people with a strong family history of cancer, arrange genetic counselling and testing where it fits, and plan the checks that follow.
Medical Oncologist
Dr. C. Raghavendra Reddy
MBBS(Gold Medal), DNB(General Medicine), DM(Medical Oncology)(Gold Medal)
Medical Oncologist
Dr. Bharati Devi Gorantla
MBBS, MD(General Medicine), DM(Medical Oncology)(Adyar,Chennai), ECMO, MRCP SCE(UK)
Medical Oncologist
Dr. Owais Mohammed
MBBS, MD (General Medicine), DrNB (Medical Oncology), ECMO, MRCP SCE (Medical Oncology) (UK)
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Sources
- American Thyroid Association (Thyroid journal) — Revised American Thyroid Association Guidelines for the Management of Medullary Thyroid Carcinoma
- GeneReviews (NCBI) — Multiple Endocrine Neoplasia Type 2
- MedlinePlus Genetics — RET gene
- MedlinePlus Genetics — Multiple endocrine neoplasia
This page is general information, not a prescription. Do not change or stop any treatment based on what you read here. If anything is worrying you, contact your own treating team — or call our helpline and we will help you reach the right specialist.
Keep reading
Related pages
The RET gene: what it doesThe basics, before the detail of codonsTesting a newborn or toddler for RETWhy RET is one of the few genes tested in early childhoodSurveillance for RET carriersWhich checks, and when, for each risk levelRET positive: what happens nextThe first weeks after a positive result
Talk to us
Not sure what risk level your family's RET result falls into?
Send us the report and tell us who in the family has been tested. We will arrange a counsellor to explain the risk level and what it means for each child. One helpline serves every CION centre.