Hereditary Retinoblastoma

Retinoblastoma (RB) is an intraocular malignancy of the developing retina associated with germline and/or somatic mutations of the RB1 tumor suppressor gene. 
Quick Reference
Test Code: 5422 Test Name: RB1 specific site analysis TAT 7-14 days Gene: 1
Test Code: 5426 Test Name: RB1 seq and del/dup TAT 14-21 days Gene: 1

Ordering Options

We now offer single site analysis (SSA) at no additional cost to family members

following single gene or panel testing* of the first family member (proband) within 90 days of the original Ambry report date.

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*excludes Secondary Findings and SNP Array tests

Why Is This Important?

  1. Option to modify age, frequency, and type of cancer screening, as needed
  2. May guide treatment and improve outcomes 
  3. Identify at-risk family members 

When To Consider Testing

  • Patients who are clinically suspected to have retinoblastoma
  • Family history of a known RB1 mutation

Mutation Detection Rate

90-92% of patients with bilateral retinoblastoma have a detectable germline mutation in the RB1 gene, whereas 13-14% of patients with unilateral retinoblastoma have a mutation in the gene (clinical sensitivity).1,2 

Ambry's RB1 analysis can detect >99.9% of described mutations in the gene, when present (analytic sensitivity).

Test Description

RB1 coding exons 1-27 and well into the 5’ and 3’ ends of all the introns and untranslated regions are analyzed by sequencing. Gross deletion/duplication analysis determines gene copy number for coding exons 1-27. Clinically significant intronic findings beyond 5 base pairs are always reported. Intronic variants of unknown or unlikely clinical significance are not reported beyond 5 base pairs from the splice junction. Genomic deoxyribonucleic acid (gDNA) is isolated from the patient’s specimen using standardized methodology and quantified. Sequence enrichment of the targeted coding exons and adjacent intronic nucleotides is carried out by a bait-capture methodology, using long biotinylated oligonucleotide probes followed by polymerase chain reaction (PCR) and next generation sequencing (NGS). Sanger sequencing is performed for any regions missing or with insufficient read depth coverage for reliable heterozygous variant detection. Reportable small insertions and deletions, potentially homozygous variants, variants in regions complicated by pseudogene interference, and single nucleotide variant calls not satisfying 100x depth of coverage and 40% het ratio thresholds are verified by Sanger sequencing. Gross deletion/duplication analysis of RB1 using multiplex ligation-dependent probe amplification (MLPA) and/or targeted chromosomal microarray is also performed.


1. Rushlow D, et al. Detection of mosaic RB1 mutations in families with retinoblastoma. Hum Mutat. 2009:30(5):842-51. 

2. Nichols KE, et al. Recent advances in retinoblastoma genetic research. Curr Opin Ophthalmol.2009;20(5):351-5. 

3. Mu W, et al. Sanger confirmation is required to achieve optimal sensitivity and specificity in next-generation sequencing panel testing. J Mol Diagn. 2016. 18(6):923-932.

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