OVERVIEW
Our laboratory offers germline panel testing via a Hereditary Cancer Multi-Gene Panel and a Pediatric Cancer Predisposition Panel. These multi-gene next-generation sequencing panel tests are available for patients known or suspected to be at risk of a cancer predisposition syndrome. For eligibility, indications, and ordering information, see our Hereditary Cancer page.
TEST REQUIREMENTS
For eligible patients:
- Completed requisition form
- 5mL EDTA peripheral blood (see Specimen Guidelines, DNA molecular test type)
For all other patients, please initiate a referral to the Hereditary Cancer Program.
TURN-AROUND TIME
Approximately 42 days from receipt of specimen and completed and signed requisition form.
RESULTS REPORTING
Germline variants are classified according to ACMG Guidelines (Richards (2015) PMID: 25741868) as one of:
- Pathogenic
- Likely Pathogenic
- Variant of Uncertain Significance (VUS)
- Likely Benign
- Benign
Please see our Variant Classification Guidelines for additional details. Benign and Likely Benign variants are not routinely reported. Only Pathogenic or Likely Pathogenic variants are reported for a subset of targeted genes (see below).
GENES TARGETED
Single nucleotide variants, small insertions and deletions, and copy number variants in the entire coding region (+/-10bp adjacent intron) in the following genes:
Hereditary Cancer Multi-Gene Panel
Entire coding region:
AIP:NM_003977*; ALK:NM_004304*; APC:NM_000038 (incl. promoter 1A); ATM:NM_000051; AXIN2:NM_004655; BAP1:NM_004656; BARD1:NM_000465; BLM:NM_000057*; BMPR1A:NM_004329; BRCA1:NM_007294 (incl. Intron 13 and 23 hotspots); BRCA2:NM_000059; BRIP1:NM_032043; CASR:NM_000388*; CDC73:NM_024529; CDH1:NM_004360; CDK4:NM_000075; CDKN1B:NM_004064*; CDKN2A:NM_000077; CHEK2:NM_007194; CTNNA1:NM_001903; DICER1:NM_177438; DIS3L2:NM_152383; EGFR:NM_005228*; FH:NM_000143; FLCN:NM_144997; GATA2:NM_032638 (incl. intron 4 hotspot)*; GPC3:NM_004484; HOXB13:NM_006361; HRAS:NM_005343*; KIT:NM_000222*; MAX:NM_002382; MEN1:NM_000244*; MET:NM_000245 (incl. Intron 13); MLH1:NM_000249 (incl. 5’UTR and Intron 12 hotspots); MSH2:NM_000251 (incl. 5’ UTR and promoter); MSH6:NM_000179; MUTYH:NM_001128425; NF1:NM_001042492; NF2:NM_000268*; NTHL1:NM_002528; PALB2:NM_024675; PDGFRA:NM_006206*; PHOX2B:NM_003924*; POT1:NM_015450*; PRKAR1A:NM_002734; PTCH1:NM_000264*; PTEN:NM_000314 (incl. promoter); RAD51C:NM_058216; RAD51D:NM_002878; RB1:NM_000321*; RET:NM_020975; SDHAF2:NM_017841; SDHB:NM_003000; SDHC:NM_003001; SDHD:NM_003002; SMAD4:NM_005359 (incl. promoter); SMARCA4:NM_001128849*; SMARCB1:NM_003073; SMARCE1:NM_003079*; STK11:NM_000455; SUFU:NM_016169*; TERC:NR_001566*; TERT:NM_198253*; TMEM127:NM_017849; TP53:NM_000546 (incl. Intron 1, 6, and 10 hotspots); TSC1:NM_000368; TSC2:NM_000548; VHL:NM_000551; WT1:NM_024426
Partial Genes:
APC:NM_001127511 (promoter 1B and exon 1); CDKN1C:NM_000076 (excl. soft masked region in exon 1); CDKN2A:NM_058195 (exon 1); CEBPA:NM_004364 (excl. soft masked region in exon 1)*; MITF:NM_000248 (codon 318; CNVs not called)*; MSH3:NM_002439 (excl. soft masked region in exon 1); PMS2:NM_000535 (exons 1-11); POLD1:NM_001256849 (exons 8-13; CNVs not called); POLE:NM_006231 (exons 9-14; CNVs not called); RUNX1:NM_001754 (excl. soft masked region in exon 9)*; SDHA:NM_004168 (excl. exon 14; CNVs not called); TP53:NM_001126113 (exon 10); TP53:NM_001126114 (exon 10)
Copy-number only:
EPCAM:NM_002354; GREM1:NM_013372
* Variants not presumed by nature or already known to be (likely) pathogenic are not reported for these genes.
Pediatric Cancer Predisposition Panel
Entire coding region:
AIP:NM_003977**; ALK:NM_004304**; ATM:NM_000051; BLM:NM_000057; BRCA1:NM_007294 (incl. Intron 13 and 23 hotspots); BRCA2:NM_000059; BRIP1:NM_032043; BUB1B:NM_001211; CD27:NM_001242*; CD70:NM_001252*; CSF3R:NM_000760*; CTLA4:NM_005214; CTR9:NM_014633*; DIS3L2:NM_152383**; DNAJC21:NM_001012339*; EGLN1:NM_022051**; EGLN2:NM_080732**; ELANE:NM_001972*; ELP1:NM_003640**; ERCC2:NM_000400**; ERCC3:NM_000122**; ERCC4:NM_005236; ERCC5:NM_000123**; ETV6:NM_001987*; FANCA:NM_000135; FANCB:NM_001018113; FANCC:NM_000136; FANCD2:NM_001018115; FANCE:NM_021922; FANCF:NM_022725; FANCG:NM_004629; FANCI:NM_001113378; FANCL:NM_018062; FANCM:NM_020937; FAS:NM_000043*; FASLG:NM_000639*; FBXW7:NM_001349798**; FH:NM_000143**; GATA2:NM_032638 (incl. intron 4 hotspot)*; GPC3:NM_004484**; GPR161:NM_001375883**; HAVCR2:NM_032782*; HAX1:NM_006118*; ITK:NM_005546*; L2HGDH:NM_024884**; LIG4:NM_206937*; MAD2L2:NM_006341; MBD4:NM_001276270; MDH2:NM_005918**; MEN1:NM_000244**; MLH1:NM_000249 (incl. 5’UTR and Intron 12 hotspots); MSH2:NM_000251 (incl. 5’ UTR and promoter); MSH6:NM_000179; PALB2:NM_024675; PAX5:NM_016734*; PHOX2B:NM_003924**; POLH:NM_006502**; PTEN:NM_000314 (incl. promoter)**; RAD51C:NM_058216; RB1:NM_000321**; REST:NM_005612**; RET:NM_020975**; SAMD9:NM_017654**; SAMD9L:NM_152703*; SBDS:NM_016038*; SH2D1A:NM_002351*; SLX4:NM_032444; SMARCA4:NM_001128849**; SMARCB1:NM_003073**; SMARCE1:NM_003079**; SUFU:NM_016169**; TP53:NM_000546 (incl. Intron 1, 6, and 10 hotspots); TRIM28:NM_005762**; TSC1:NM_000368**; TSC2:NM_000548**; UBE2T:NM_014176; VHL:NM_000551**; WT1:NM_024426**; XPA:NM_000380**; XPC:NM_004628**; XRCC2:NM_005431
Partial genes:
CDKN1C:NM_000076 (excl. soft masked region in exon 1)**; CEBPA:NM_004364 (excl. soft masked region in exon 1)*; MITF:NM_000248 (codon 318, CNVs not called)**; MSH3:NM_002439 (excl. soft masked region in exon 1); PMS2:NM_000535 (exons 1-11); RUNX1:NM_001754 (excl. soft masked region in exon 9)*; TP53:NM_001126113 (exon 10); TP53:NM_001126114 (exon 10)
Reduced sensitivity targets:
Due to low mapping quality, this assay has reduced sensitivity and may not be able to call variants in the following targets: SLX4:NM_032444 (exon 13); FANCD2:NM_001018115 (exons 1-14, exon 17, exon 22)
* For patients presenting with solid tumours, variants not presumed by nature or already known to be (likely) pathogenic are not reported for these genes.
** For patient presenting with a hematologic malignancy, variants not presumed by nature or already known to be (likely) pathogenic are not reported for these genes.