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BRCA1 large rearrangements, and why a panel can miss them | CION Cancer Clinics
A large rearrangement is a BRCA1 fault where a whole block of the gene is missing or doubled. A test that only reads the gene letter by letter can miss it, unless the laboratory also counts copies of each block. This page explains what these faults are, how laboratories find them, and how to check whether your own test looked for one. 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
- What is a BRCA1 large rearrangement, and how can a test miss it?
- What kinds of large rearrangement are there?
- How does a laboratory look for a missing block?
- The words you will meet, in plain language
- A test that reads letters only, versus a complete BRCA1 test
- Four things families tell us, and what is actually true
- What this page cannot tell you
- Common questions about BRCA1 large rearrangements
The short answer
What is a BRCA1 large rearrangement, and how can a test miss it?
A large rearrangement is a BRCA1 fault where a whole block of the gene is missing or copied twice, rather than one letter being wrong. Many tests read the gene letter by letter and are not built to notice a missing block. Unless the laboratory also runs a separate check for deletions and duplications, this kind of fault can be missed.
Why this is not a rare technical detail
In BRCA1 in particular, large rearrangements make up a real share of the harmful faults found in families. The share varies between populations and between studies, but it is large enough that every major guideline expects a proper BRCA1 test to look for them. A test that skips this step is incomplete, however clean the report looks.
Why it matters to your family
A missing block in BRCA1 usually breaks the gene just as surely as a spelling error does. If it is missed, a family with a strong pattern of breast and ovarian cancer may be told nothing was found. Relatives then lose the chance of a simple, targeted test and of earlier checks.
A large rearrangement that breaks the gene carries broadly the same risk as any other harmful BRCA1 fault.What the lab may find
What kinds of large rearrangement are there?
Genes are built in sections called exons. A rearrangement is described by which sections are affected and how.
Deletion
One or more exons are simply missing. The cell cannot build a working BRCA1 protein from what is left. Most large rearrangements reported in families are deletions, and most are treated as harmful.
Duplication
A block of the gene appears twice. Whether this breaks the gene depends on where the extra copy sits. Some duplications are clearly harmful, while others are reported as uncertain until more is known.
Often reported as
- Pathogenic, when the extra copy sits inside the gene
- Uncertain, when its position is not yet clear
Whole-gene deletion
Occasionally one whole copy of BRCA1 is missing. The effect on the cell is much the same as any other harmful fault, because one working copy has been lost from birth.
Why letter-by-letter reading misses them
When one copy of a block is missing, the other copy is still there and reads perfectly. The test sees normal letters and has no reason to raise an alarm. Only a method that counts copies can spot what is absent.
Not sure whether this applies to you?
Ask an oncologistInside the laboratory
How does a laboratory look for a missing block?
The gene is read letter by letter
Modern sequencing reads every exon of BRCA1 and catches spelling errors, small missing letters and small extra letters. This is the part most people picture when they think of a gene test.
Copies of each block are counted
A second analysis asks a different question: are there two copies of every exon, as there should be? This is called deletion and duplication analysis. It can be done from the sequencing data itself or with a dedicated test.
A suspected change is confirmed
If one exon appears to have one copy or three, good laboratories confirm it with a second method before reporting. A common one is called MLPA, which measures the number of copies of each exon directly.
The finding is classified and reported
The laboratory decides whether the change is harmful, uncertain or harmless, and writes the exact exons involved on the report. That precise description is what relatives are later tested for.
On your report
The words you will meet, in plain language
- Exon
- One of the sections a gene is built from. BRCA1 has many, and a rearrangement names which ones are affected.
- Large rearrangement
- A fault involving a whole block of the gene rather than a single letter. It may also be written as a large genomic rearrangement.
- Deletion and duplication analysis
- The part of a test that counts copies of each exon. Look for these words, or the short form del/dup, on your report.
- Copy number
- How many copies of a stretch of DNA are present. Normally two, one from each parent.
- MLPA
- A laboratory method that counts copies of each exon. It is widely used to find or confirm large rearrangements.
- Pathogenic
- Known to break the gene and raise cancer risk. A harmful BRCA1 rearrangement is reported with this word.
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Side by side
A test that reads letters only, versus a complete BRCA1 test
Letters only
Letters plus copy counting
Finds spelling errors in the gene
Finds spelling errors and missing or extra blocks
A negative result leaves a gap
A negative result is far more reliable
Common in some older or cheaper tests
The expected standard for BRCA1 testing today
May need repeating if the family history is strong
Rarely needs repeating for BRCA1 itself
Commonly believed
Four things families tell us, and what is actually true
"My BRCA1 test was negative, so the gene is fine."
That depends on what the test covered. If it read the letters but never counted copies, a missing block could still be there. The report, or the laboratory, can tell you which methods were used.
"A big missing piece must be more dangerous than a small error."
Size does not decide risk. What matters is whether the gene still works. A single wrong letter and a missing block can both switch BRCA1 off, and both are managed the same way.
"All modern panels check for rearrangements automatically."
Most good panels do, but not every test on the market says so clearly. Some low-cost tests and some older reports cover only the letters. It is always worth checking rather than assuming.
"If one relative had a full test, nobody else needs one."
Once a rearrangement is found, relatives are tested for that exact change. If the first test in the family was negative and incomplete, the gap applies to everyone who relied on it.
Being straight with you
What this page cannot tell you
It cannot tell you whether your earlier test looked for large rearrangements. Reports differ in how clearly they say so. Some list the method in small print near the end, and some leave it out altogether. A counsellor can read the report and, if needed, ask the laboratory directly what was covered.
It cannot tell you what a rearrangement means for you
A report that names a deleted or duplicated exon is written for the doctor who ordered it. What your specific variant means is a question for the counsellor who ordered the test. This is especially true of duplications, where the answer can depend on details a report cannot show at a glance.
Who this does not apply to
Most people reading this do not need a BRCA1 retest. If your family has no pattern of young breast cancer, ovarian cancer or male breast cancer, testing is unlikely to help, whatever the method. And if your test already included deletion and duplication analysis, there is nothing to add for this gene.
Unsure what your earlier test covered? Call the helpline and someone will help you check.Questions we are asked
Common questions about BRCA1 large rearrangements
How do I know if my test checked for large rearrangements?
Look on the report for words such as deletion and duplication analysis, copy number, del/dup or MLPA. If none appear, the laboratory can confirm what was done. A genetic counsellor can also read the report with you and explain what was and was not covered.
Should I be retested if my old test missed this step?
Only if your family history makes a BRCA1 fault a real possibility. If it does, a counsellor may suggest a fuller test that counts copies as well as reading letters. Often only the missing step needs adding, and the whole test does not have to be repeated.
Is a large rearrangement treated differently from other BRCA1 faults?
Not once it is confirmed as harmful. Screening, risk-lowering options and treatment choices are the same as for any other harmful BRCA1 fault. What differs is only the laboratory method used to find it and to test relatives.
How are my relatives tested for a rearrangement?
Each relative is tested for the exact block found in your family, usually with a copy-counting method such as MLPA. This targeted test is simpler than the first one. The laboratory needs your report to know exactly what to look for, so keep a copy safe.
My report says duplication of uncertain significance. What now?
It means the laboratory cannot yet say whether the extra copy breaks the gene. It should not change your care or lead to preventive surgery on its own. Your plan follows your family history, and the finding may be reclassified as evidence grows.
Are large rearrangements more common in Indian families?
Indian studies have found them among BRCA1 carriers, but the studies are small and mostly from city hospitals. Nobody can yet give a reliable Indian figure. What is clear is that they occur here, so a complete test should look for them.
Can a tumour test find a large rearrangement?
A tumour test answers a different question, about changes inside the cancer, and may not be designed to count copies in the inherited gene. For inherited risk, a blood or saliva test with deletion and duplication analysis is the right tool.
Does this apply to BRCA2 and other genes too?
Large rearrangements happen in many cancer genes, including BRCA2 and the bowel cancer genes. In BRCA2 they appear to be less common than in BRCA1. A good panel counts copies across every gene it tests, not just BRCA1.
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
- GeneReviews (NCBI) — BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer
- National Cancer Institute — Genetics of Breast and Gynecologic Cancers (PDQ)
- National Cancer Institute — BRCA Gene Changes: Cancer Risk and Genetic Testing
- MedlinePlus Genetics — BRCA1 gene
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
Indian founder variants in BRCA1Why a short list of common faults is not enough in IndiaA variant of uncertain significance in BRCA1What to do with an uncertain result, including duplicationsSurveillance for BRCA1 carriersThe checks that follow once a fault is confirmedBRCA1 vs BRCA2: how the risks actually differHow the two genes compare once a fault is found
Talk to us
Not sure whether your BRCA1 test counted copies?
Bring your report, and a genetic counsellor can check exactly which methods were used and whether anything needs adding. Counselling is available in Telugu. One helpline serves every CION centre.