We offer family variant testing for all blood relatives of patients who undergo full single gene sequencing, multigene panel testing or exome sequencing at Ambry Genetics and are found to have a pathogenic or likely pathogenic variant. Testing must be completed within 90 days of the original report date. Whenever possible, more closely related relatives should be tested before more distant relatives. If you or a family member are interested in learning more about our family testing program or when family testing may be clinically indicated, please contact us or your provider for additional information. Note that Ambry can only provide such family testing services to patients receiving medical care in the U.S or US territories.
Order NowBased on published guidelines1, APC genetic testing should be considered for any of the following:
Prevalence of APC mutations among those with polyposis depends on the phenotype.2
Detection rates are highest in those with classic FAP and those with a family history of polyposis (clinical sensitivity). Ambry's APC analysis can detect >99.9% of described mutations in the gene, when present (analytic sensitivity).
APC coding exons 1-15 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 1-15. Additionally, all promoter 1B gross deletions as well as single nucleotide substitutions within the promoter 1B YY1 binding motif are analyzed and reported. 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. Potentially homozygous variants, variants in regions complicated by pseudogene interference, and variant calls not satisfying depth of coverage and variant allele frequency quality thresholds are verified by Sanger sequencing. Gross deletion/duplication analysis of APC using read-depth from NGS data is also performed. Any copy number changes detected by NGS are confirmed by targeted chromosomal microarray and/or multiplex ligation-dependent probe amplification (MLPA).
1. Syngal S, et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015. 110(2):223-62.
2. Grover S, et al. Prevalence and phenotypes of APC and MUTYH mutations in patients with multiple colorectal adenomas. JAMA. 2012. 308(5):485-492.