PMC Hereditary Cancer Panel

Associated Conditions
- APC-associated polyposis conditions
- Ataxia telangiectasia (A-T)
- Hereditary breast and gynecologic cancers
- Oligodontia-colorectal cancer syndrome
- Juvenile polyposis syndrome (JPS)
- Hereditary breast and ovarian cancer syndrome (HBOC)
- BAP1 tumor predisposition syndrome
- Hereditary diffuse gastric cancer syndrome
- CDK4-related cutaneous melanoma
- Melanoma-pancreatic cancer syndrome and melanoma-neural system tumor syndrome
- DICER1-related pleuropulmonary blastoma familial tumor predisposition syndrome
- Lynch syndrome
- Constitutional mismatch repair deficiency (CMMR-D)
- FH tumor predisposition syndrome
- Hereditary mixed polyposis syndrome
- HOXB13-related predisposition to prostate cancer
- Familial GIST, familial mastocytosis
- Multiple endocrine neoplasia type 1
- MSH3-associated polyposis
- MUTYH-associated polyposis (MAP)
- MBD4-associated neoplasia syndrome (MANS)
- NF1-related conditions
- NTHL1-associated polyposis
- GIST-plus syndrome
- Polymerase proofreading–associated polyposis (PPAP)
- PTEN hamartoma tumor syndrome
- Hereditary paraganglioma-pheochromocytoma syndrome
- Small cell carcinoma of the ovary, hypercalcemic type
- Peutz-Jeghers syndrome
- Li-Fraumeni syndrome
- Tuberous sclerosis complex
- von Hippel-Lindau syndrome
- Predisposition to ovarian cancer, endometrial cancer, and prostate cancer
- Cowden syndrome and Cowden-like syndrome
- Myeloid malignancy
- Dominant familial platelet
- Hereditary paraganglioma-pheochromocytoma (PGL-PCC) syndrome and renal cancer

Methodology

Targeted Exome/ Slice Exome (Next Generation Sequencing including Copy Number Variation)

Coverage

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Assay Information
- MUTYH (RNA): Sensitivity to detect RNA splice variants involving exons 2-3 may be reduced.
- CDH1 (RNA): Sensitivity to detect RNA splice variants involving exons 1-3 may be reduced.
- PMS2 (RNA): Sensitivity to detect RNA splice variants involving exons 11-15 may be reduced.
- TSC2 (RNA): Sensitivity to detect RNA splice variants involving exons 25-27 may be reduced.
- MLH1: Deletion/duplication analysis covers the promoter region. Sequencing analysis for exons 12 includes only cds +/- 10 bp.
- MSH6: Sequencing analysis for exons 7| 10 includes only cds +/- 10 bp.
- DICER1: Sequencing analysis for exons 22 includes only cds +/- 10 bp.
- NF1: Sequencing analysis for exons 2| 7| 25| 41| 48 includes only cds +/- 10 bp.
- TP53: Deletion/duplication analysis covers the promoter region.
- BMPR1A: Deletion/duplication analysis covers the promoter region.
- MSH3: Sequencing analysis of the repeat region of exon 1 (5:79950697-79950765) is not offered.
- ATM: Sequencing analysis for exons 6| 24| 43 includes only cds +/- 10 bp.
- POLD1: Sequencing analysis for exon 22 includes only cds +/- 10 bp and exon 27 includes only cds +-0 bp.
- FH: Sequencing analysis for exons 9 includes only cds +/- 10 bp.
- APC: The 1B promoter region is covered by both sequencing and deletion/duplication analysis. The 1A promoter region is covered by deletion/duplication analysis. Sequencing analysis for exons 5 includes only cds +/- 10 bp.
- BRCA1: Sequence analysis includes +/- 20 base pairs of adjacent intronic sequence.
- MSH2: Analysis includes the exon 1-7 inversion (Boland mutation). Sequencing analysis for exons 2| 5 includes only cds +/- 10 bp. Deletions restricted to only the EPCAM gene will not be detected unless EPCAM analysis is requested.
- GREM1: Promoter region duplication testing only.
- PMS2: Sequencing analysis for exons 7 includes only cds +/- 10 bp.
- TSC1: Sequencing analysis for exons 21 includes only cds +/- 10 bp.
- PTEN: Sequencing analysis for exons 8 includes only cds +/- 10 bp.
- SDHA: Deletion/duplication analysis is not offered for this gene and sequencing analysis is not offered for exon 14. Sequencing analysis for exons 6-8 includes only cds +/- 10 bp.
- SDHC: Sequencing analysis for exons 2| 6 includes only cds +/- 10 bp.
- MEN1: Sequencing analysis for exons 2 includes only cds +/- 10 bp.
- EPCAM: Sequencing analysis is not offered for this gene.
- BRCA2: Sequence analysis includes +/- 20 base pairs of adjacent intronic sequence.

Reflex Test

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Ordering information

Turnaround Time: 10-14 business days

New York Approved: Yes

Preferred Speciment: 3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)

Alternate Specimens: Saliva Kits (available upon request) or 3-mL whole blood in purple top EDTA tube or Nail clippings

Learn more about specimen requirements Request a specimen collection kit

Limitations

All sequencing technologies have limitations. A negative result from this analysis does not rule out a possible genetic diagnosis as some variants may not be detected by this test. This test is not designed to detect low level mosaicism, structural rearrangements, indels >40bp, deep intronic variants of unknown clinical significance, or large cytogenetic CNVs. Certain inherent qualities of the human genome, for example repetitive regions/homopolymers, GC rich, pseudogenes, and rare polymorphisms, pose significant technical challenges such as sequence misalignment that may potentially impact the accuracy of the results. False negative results may also occur in the setting of allogeneic bone marrow, stem cell transplantation, active or chronic hematologic conditions, recent blood transfusions, suboptimal DNA quality or PCR trace contamination. Other potential sources of error include sample mix-ups and clerical issues.

References
- References
- 1. Richards S et al. Genetics in medicine. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. 2015 May;17(5):405-24 (PMID: 25741868)
- 2. GnomAD (gnomAD)
- 3. CSPEC (ClinGen variant classification rules registry) Criteria Specification Registry
- 4. Normal copy number variation in healthy individuals database of genomic variants: http://dgv.tcag.ca/dgv/app/home
- 5. Riggs, E.R., Andersen, E.F., Cherry, A.M. et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med 22, 245–257 (2020). https://doi.org/10.1038/s41436-019-0686-8
- 6. Landrum MJ, Lee JM, Riley GR, Jang W, Rubinstein WS, Church DM, Maglott DR. ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res. 2014 Jan 1;42(1):D980-5. doi: 10.1093/nar/gkt1113. PubMed PMID: 24234437.
- 7. Online Mendelian Inheritance in Man, OMIM®. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD), Copyright® 1966-2012. World Wide Web URL: http://omim.org.
- 8. http://tinyurl.com/ACMGv4 (ACMG/ Clingen draft Interpretation SOP); clingen_variant-curation_sopv1.pdf

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Test Description

Associated Conditions

Methodology

Coverage

Assay Information

Reflex Test

Ordering information

Limitations

References

Tagged Genes