Submitted in Familial Cancer

Validation of Three BRCA1/2Mutation-Carrier ProbabilityModels MYRIAD, BRCAPRO and BOADICEA in a Population-Based Series of 183 German Families

S.M. Schneegans1* , A. Rosenberger2*, U. Engel1, M. Sander3, G. Emons3 andM. Shoukier 1

* Both authors contributed equally to this work.

1Institute of Human Genetics,UniversityMedicalCenter, Georg August University Göttingen, Heinrich-Düker-Weg 12, 37073 Göttingen,Germany

2Department of Genetic Epidemiology, University Medical Center, Georg August University Göttingen,Humboldtallee 32, 37073 Göttingen, Germany

3Department of Gynecology and Obstetrics, University Medical Center, Georg August UniversityGöttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany

Correspondence to: Moneef Shoukier, University of Göttingen, Institute of Human Genetics, Heinrich-Düker-Weg 12, 37073 Göttingen, Germany,Tel. +49 551 39 7593, Fax +49 551 39 7567. e-mail: .

Online Resource 1Mutations detected in our patient collective listed with family members affected by breast and/ or ovarian cancer with age at diagnosis and personal risk figures calculated by BRCAPRO, BOADICEA and MYRIAD. The nomenclature for these mutations is based on the NCBI reference sequence U14680.1 for mRNA of BRCA1, or U43746.1 for mRNA of BRCA2. The first nucleotide of mRNA is numerated as 1 in accordance with BIC nomenclature.

Pat.-ID / Nucleotide Change in BRCA1 / The Family History for BC with Age at Diagnosis in Years / The Family History for OC with Age at Diagnosis in Years / Risk BRCAPRO
(%) / Risk BOADICEA
(%) / Risk MYRIAD
(%)
26986 / c.185_186delAG / Pat. 46 / Pat. 44,
grandmother (pa) 36 / 91.00 / 89.44 / 66.00
26974 / c.185_186delAG / Sister 45 / Pat. 42 / 66.50 / 64.79 / 23.10
26971 / c.185_186delAG / Pat. bilat. 45+ 51,
mother 47 / 97.10 / 90.90 / 12.20
11187* / c.185_186delAG / Pat. 38,
sister bilat. 36+ 41, / 69.50 / 45.84 / 15.80
11176* / c.300 T>G / Pat. 40,
aunt (m)40 / 2.30 / 8.20 / 15.80
22128* / c.300 T>G / Pat. bilat. 51+ 64,
daughter 44,
3 sisters 60, 57, 50,
Niece bilat. 35 + 39 / 99.00 / 92.63 / 11.40
26990 / c.862delC / Pat. 36,
aunt (pa) 39 / 2 Aunts (pa) 71, 42 / 87.00 / 84.47 / 39.20
11145* / c.1406insA / Pat. bilat. 50+ 70,
daughter 65,
mother 49,
2 nieces / Daughter 59,
sister 63 / 99.60 / 87.03 / 15.90
26929 / c.2115delC / Pat. 28 / Grandmother (m) 48 / 26.30 / 19.67 / 16.90
30073 / c.2494delC / Pat. 57,
sister bilat. 40+ 45 / Pat. 57,
mother 57,
sister 50 / 99.6 / 93.61 / 60
30082 / c.2594delC / Pat. 21 / Grandmother (m) 75, grandaunt (m) 65 / 25.4 / 9.91 / 16.9
11128* / c.3519G>T / Pat. 48,
mother 45,
aunt (m)54 / 63.80 / 41.98 / 15.80
30035 / c.3600delGAAGATACTAG / Pat. 34,
grandmother (m) 42 / 8.20 / 12.88 / 15.80
32301 / c.3604delA / Pat. 50,
mother 38,
grandmother (m) 39,
grandaunt (m) 50 / 38.60 / 29.44 / 11.40
26988 / c.3746-3747ins A / Pat. bilat. 44+ 51,
aunt (m) 39 / Mother 65,
aunt (m) 35 / 99.00 / 96.93 / 39.20
26941 / c.del3819-3823GTAAA / Sister 40 / Pat. 63,
2 sisters 72, 32 / 94.30 / 89.26 / 46.50
11198* / c.3819-3823delGTAAA / Pat. bilat. 33+ 43,
mother 45,
grandaunt bilat. 67 / Mother 46 / 99.20 / 98.33 / 39.20
30095 / c.4086C>T / Pat. bilat. 39+ 64,
grandmother (pa) bilat. 60+ 65 / 97.9 / 51.1 / 2.8
26935 / c.4794+1G>A / Mother 55 / Pat. 75,
mother 54 / 53.50 / 34.61 / 21.10
30064 / c.4808C>G / Pat. 48 / Mother 48 / 13.1 / 30.06 / 16.9
11147* / c.4808C>G / Pat.bilat. 37+ 38,
sister 40,
mother 58, / Pat. 42,
sister 41 / 100.00 / 99.74 / 79.00
26917 / c.5105+6T>G / Pat. 49,
grandmother (m) 54, grandaunt 54 / Mother 54 / 26.10 / 36.88 / 16.90
11168* / c.5149delCTAA / Pat. 53,
3 Sisters 45, 50, 50,
mother bilat. 64,
aunt (m) 60,
grandmother (m) bilat. 68 / Mother 66 / 85.00 / 80.36 / 15.90
11122* / c.5298A>T / Pat. 51,
2 sisters 38, 27 / 49.20 / 28.29 / 11.40
32313 / c.5382_5383insC / Pat. 40 / Pat. 40 / 39.80 / 64.46 / 39,10
11112* / c.5382_5383insC / Pat. bilat. 39+ 61,
daughter 41 / 25.70 / 25.41 / 15.80
30084 / c.5382_5383insC / Pat. 37,
sister 50 / Pat. 38,
2 Sisters EC or OC 49,50 / 99.9 / 99.92 / 70.8
30024 / c.5382_5383 ins C / Pat. 41,
mother 45,
aunt (m) bilat. 50+ 61, grandmother (m) 43,
grandaunt (m) 50,
second cousin (m) 50 / Grandaunt 25 / 81.70 / 47.87 / 30.10
26987 / c.5382_5383insC / Pat. 38 / Mother 56,
grandmother (m) 85 / 58.60 / 21.49 / 27.30
26946 / c.5382_5383insC / Pat. bilat. 39,
daughter 32,
mother 65,
aunt (m)70,
Cousin (m) ? / 94.80 / 90.24 / 15.80
22130* / c.5382_5383insC / Pat. 39,
aunt (pa) 58,
aunt (pa) EC or OC 58 / 68.50 / 67.63 / 33.20
11162* / c.5382_5383insC / Pat. 55,
daughter 38 / 2 Daughters 40, 38 / 67.10 / 84.98 / 15.90
26900 / Ex. 1-4 del / Pat. bilat. 41+ 63,
daughter 41,
Aunt (m) 70,
Cousin bilat. 51+ 56 / Aunt (m) EC or OC 54 / 71.00 / 84.05 / 39.20
30081 / Ex. 2 del / Pat. 27,
mother bilat. 31+ 33, grandmother (pa) 70 / Mother 42 / 97.9 / 97.56 / 39.2
32310 / Dup Ex. 13 / Pat. bilat. 42+ 45,
sister bilat. 29,
grandaunt (m) ? / Pat. 49, Mother 69 / 100.00 / 99.97 / 79.00
Pat.-ID / Nucleotide Change in BRCA2 / The Family History for BC with Age at Diagnosis in Years / The Family History for OC with Age at Diagnosis in Years / Risk BRCAPRO / Risk BOADICEA / Risk MYRIAD
30068 / c.886delGT / Pat. 56,
mother 38 / Pat. 42 / 82.2 / 79 / 26.1
26970 / c.del16174T / Pat. 32,
grandmother bilat. (pa) 30 / 85.10 / 79.11 / 53.90
11161* / c.4457insA / Pat. 81,
daughter 47 / 6.20 / 0.35 / 21.10
32319 / c.4512insT / Pat. 67,
mother 50 / 0.60 / 1.76 / 2.90
30054 / c.4512insT / Pat. 35,
cousin (?) ? / Cousin(?)? / 3.8 / 4.14 / 6.8
20342* / c.4781delA / Grandmother (m) bilat. 47,
3 grandaunts (m) 25,50,65 / 5,30 / 4,96 / 4,50
30003 / c.5392-5393delAG / Pat. bilat. 44,
mother 40 / Pat. 66,
grandmother (m) EC or OC 65 / 99.90 / 98.48 / 79.00
26956 / c.5467insT / Pat. 49,
mother bilat. 74 / Pat. 60 / 16.10 / 77.06 / 39.10
11142* / c.5803delATTA / Pat. 54,
2 sisters 59, 48 / Pat. 46,
aunt (pa) 60 / 90.10 / 85.73 / 60.00
30005 / c.7253-7254delAA / Pat. 45,
sister 32,
mother 51 / 57.10 / 31.49 / 15.80
11205* / c.9631delC / Pat. bilat. 33+ 46,
sister 27 / 87.60 / 73.45 / 15.80
11209 / Ex. 15- 16 dup / Mother 45,
2 aunt (m)73, 41
cousin (m) 50
daughter of cousin (m) 22 / 34.20 / 25.77 / 8.70
26918 / Ex. 22- 27 del / Pat. 34 / 1.20 / 3.00 / 6.80

Aberrations: BC, breast cancer; bilat., bilateral; del, deletion; dup, duplication; ins,insertion; EC or OC, either an endometrial cancer or an ovarian cancer (uncertain); ex. , exon; OC, ovarian cancer; m,maternal; pa, paternal; pat., patient; *patient from group1.