Short answer
RET codon and variant names can help route follow-up, but they should not be used alone. The same report should also be checked for germline versus tumor context, pathogenic versus VUS classification, MEN2 phenotype language, sample type, and whether family testing is appropriate. Codon 918, codon 634, V804M, and codons 609, 611, 618, and 620 often point to different counseling questions, but the exact variant and clinical context decide the next step.
How to compare variants
| Report clue | Common concern | Useful next page |
|---|---|---|
| M918T or codon 918 | MEN2B language, early timing, and whether the finding is germline or tumor-only | RET codon 918 MEN2B questions |
| Codon 634 | MEN2A context, pheochromocytoma and parathyroid planning, family testing | RET codon 634 MEN2A questions |
| V804M | Moderate-risk language, familial medullary thyroid cancer context, exact variant wording | RET V804M variant interpretation |
| Codons 609, 611, 618, or 620 | MEN2A/FMTC patterns, variant-specific risk category, cascade testing | RET codon 609, 611, 618, and 620 questions |
| C609Y or C618R | Exact variant wording, germline confirmation, sample type | RET C609Y and C618R report questions |
| Variant of uncertain significance | Reclassification and avoiding premature family testing | RET VUS family testing questions |
What changes the next step
The next step changes if the result came from tumor-only testing instead of germline testing, if paired tumor-normal testing used a limited normal comparator, if the report suggests mosaicism, or if the variant is uncertain rather than pathogenic or likely pathogenic. GeneReviews notes that MEN2 molecular diagnosis depends on a germline RET pathogenic or likely pathogenic variant, and that a RET VUS does not establish or rule out the diagnosis.
What not to do
Do not turn a codon number into a family-testing plan without checking the exact variant and report type. Do not treat a tumor-only RET finding as proof of inherited MEN2 risk. Do not use a VUS as a known family variant. Do not assume two RET variants with similar-looking names have the same surveillance timing or family implications.
Questions to ask
- What is the exact RET variant, including codon and amino acid change?
- Does the report say pathogenic, likely pathogenic, VUS, somatic, germline, suspected germline, or mosaic?
- Was this result from tumor-only, paired tumor-normal, or dedicated germline testing?
- Does the report connect the variant to MEN2A, MEN2B, FMTC, or another clinical context?
- Who will translate the variant into surveillance timing and family testing?
When follow-up matters more
Follow-up matters more when a hereditary tumor result could change who in the family should be tested, when tumor-only and germline questions are still mixed together, or when a specialist plan should decide surveillance timing rather than a single lab result. Genetics counseling helps keep the finding tied to the actual family question.
FAQ
Can a codon number alone tell MEN2A from MEN2B?
No. Codon numbers help route the question, but the exact amino acid change, report type, and clinical context still matter.
Is M918T always MEN2B?
M918T is strongly associated with MEN2B, but the report still needs to be read as germline or tumor and interpreted in context.
Why can similar RET codons have different counseling?
Different codons can carry different risk categories, ages of onset, and family-testing implications.
What if the report says VUS?
A VUS is not enough to make a family testing or surveillance plan by itself.
Should tumor-only RET results be used for family testing?
Not without germline confirmation. Tumor-only findings do not automatically prove inherited risk.
Who should explain the variant to relatives?
A genetics professional or the ordering specialist should translate the variant into family testing and surveillance steps.
Related guides: RET risk category interpretation, RET result follow-up roadmap, MEN2 surveillance after positive RET testing, and MEN2 family variant testing.