Author, Year Country BRCA Coverage Screening Method # of mutationsa N Study inclusion criteria Ref. BRCA1 BRCA2 Abugattas, 2014 Peru HISPANEL-114 mutations Sequencing 4 1 266 unselected breast cancer patients, diagnosed at any age [49] Anton Culver, 2000 USA-Hispanics BRCA1: 185delAG, 5382insC, R1443X, int5-11T-G, R841W,4184delTCAA, 2594delC ASO 0 N/A 42 unselected breast cancer patients, greater than 18 years old [51] Carraro, 2011 Brazil BRCA1 and BRCA2: Allexons and adjacent intronic regions Sequencing 8 10 54 unselected breast cancer patients, aged 35 years or younger at the time of diagnosis [33] Delgado, 2011 Uruguay BRCA1 and BRCA2: Allexons and adjacent intronic regions HDA, PTT, Sequencing 7 14 42 1) at least three cases of female breast cancer with at least one of them diagnosed before the age of 50 2) two cases of female breast cancer at least one diagnosed before 50 years old and at least one of the following additional criteria: paternal transmission, bilateral breast cancer, ovarian cancer, male breast cancer. [50] Dufloth, 2005 Brazil BRCA1: exon 2, 3, 5, 11, 20 BRCA2: exon 10, 11" SSCP, sequencing 1 2 31 1) early onset (at less than 45 years of age) and/or bilaterality 2) more than three cases of breast cancer and more than one case of ovarian cancer in the family 3) more than two first-degree relatives involved 4) male breast cancer [34] Esteves, 2009 Brazil BRCA1: exon 11 BRCA2: exon 10, 11 PTT, sequencing 7 3 612 1) women with a history of two or more relatives with breast and/or ovarian cancer along three or more generations 2) two or more cases of breast and/or ovarian cancer in first-degree relatives 3) male relatives with breast cancer diagnosed under 35 years of age 4) cases of bilateral breast cancer [35] Ewald, 2011 Brazil BRCA1: 185delAG, 5382insC BRCA2: 6174delT PCR 1 0 131 1) the American Society of Clinical Oncology (ASCO) criteria for HBOC 2) a prior probability of harboring a BRCA mutation ≥ 30% by pedigree analysis using the Myriad mutation prevalence tables or the Penn II mutation prediction model 3) Women diagnosed with bilateral breast cancer under the age of 50 years, regardless of family history [36] Gallardo, 2006 Chile BRCA1 and BRCA2: covering coding sequences and intron-exon boundaries (exons 2 to 24) PCR, SSCP, PTT, HDA, sequencing 15 11 54 1) three cases of breast cancer in first degree relatives 2) two cases of breast cancer in first degree relatives, one diagnosed before age 40 3) one breast cancer and one ovarian cancer in first degree relatives [39] Garcia-Jimenez, 2012 Costa Rica BRCA1: exon 11 BRCA2: exon 10, 11 PTT 1 2 116 1) least three individuals diagnosed with breast cancer at any age or ovarian cancer on one side of the family 2) at least two individuals diagnosed with breast cancer under the age of 50 on one side of the family [48] Gomes, 2007 Brazil BRCA1: exon 11 BRCA2: exon 10, 11 PTT, sequencing 2 2 402 unselected breast cancer patients [37] Gonzalez-Hormazabal, 2011 Chile BRCA1 and BRCA2: Allexons and adjacent intronic regions CSGE, HDA, Sequencing 30 25 326 1) Three or more family members with breast and/or ovarian cancer 2) Two family members with breast cancer 3) One family member with breast cancer and one with ovarian cancer 4) Single affected individual with breast cancer greater than or equal to age 35 5)  Single affected individual with breast cancer greater than or equal to age 50 6) Single affected individual with male breast cancer [40] Hall, 2009 USA-Hispanics BRCA1 and BRCA2: Allexons and adjacent intronic regions Myraidb 5 2 1936 Persons undergoing clinical full-sequence for BRCA1/2 mutations at Myraid Genetics Inc. from November 1996 to March 2006 [16] Hernandez, 2014 Colombia BRCA1: exon 11 BRCA2: exon 10, 11 PTT, sequencing 2 1 244 unselected breast cancer patients, diagnosed at any age [43] John, 2007 USA-Hispanics BRCA1: All exons and adjacent intronic regions CSGE, 2DGS, Myraidb 11 N/A 393 A: patients whose cancers are likely to be hereditary 1) breast cancer diagnosis before age 35 years 2) bilateral breast cancer, with first diagnosis before age 50 years 3) prior ovarian or childhood cancer 4) at least 1 first-degree relative with breast or ovarian cancer. B: all other patients with cancers less likely to be hereditary [52] Judkins, 2012 USA-Hispanics BRCA1 and BRCA2: All Large genomic rearrangements multiplex PCR, Myraidb       1) invasive or in situ breast cancer diagnosed under age 50 years, or ovarian cancer 2)male breast cancer diagnosed at any age, in conjunction with 2 or more relatives similarly affected 3) breast cancer patient with no deleterious mutation detected by BRCA1/2 sequencing [53] Lara, 2012 Venezuela BRCA1: All exons and adjacent intronic regions CSGE, sequencing 24 30 58 1) early onset (less than 45 years of age) and/or bilaterality 2) more than three cases of breast cancer and more than one case of ovarian cancer in the family 3) more than two first-degree relatives affected 4) male breast cancer [17] Nahleh, 2015 Mexico BRCA1 and BRCA2: All exons and adjacent intronic regions Myraidb 11 5 88 unselected breast cancer patients, diagnosed at any age [28] Ruiz-Flores, 2002 Mexico BRCA1 and BRCA2: All exons and adjacent intronic regions HDA, Sequencing 3 7 51 1) breast cancer diagnosed at age 35 or younger, with no first or second-degree relatives affected with breast or ovarian cancer 2) two cases or more of breast cancer with at least one case diagnosed under 60 among first and second-degree relatives 3) one case of breast cancer under 60 and one case of ovarian cancer diagnosed at any age in first and second degree relatives 4) one case of female and one case of male breast cancer diagnosed at any age in first degree relatives [18] Sanabria, 2009 Colombia BRCA1: 185delAG, 5382insC PCR 0 N/A 30 1) Woman of any age with diagnostics of BC 2) With Family background in first or second degree 3) Woman with diagnostics of BC under 36 year’s old, Without Family background [44] Sanchez, 2011 Chile BRCA1 and BRCA2: only Large Genomic rearrangements MLPA 2 0 74 1) three cases of breast cancer in first degree relatives 2) two cases of breast cancer in first degree relatives, one diagnosed before age 40 3) one breast cancer and one ovarian cancer in first degree relatives [41] Silva, 2014 Brazil BRCA1 and BRCA2: All exons and adjacent intronic regions Sequencing, MLPA 18 6 120 1) Breast cancer diagnosed ≤45 years of age (no family history) 2) Breast cancer diagnosed ≤ 45 years of age with 1 or more close blood relative with breast/ovarian/fallopian tube/primary peritoneal cancer at any age 3) Breast cancer diagnosed <45 ≤ 50 years of age with 1 or more blood relative with breast/ovarian/fallopian tube/primary peritoneal cancer ≤ 50 years of age 4) Breast cancer diagnosed >50 of age with 1 or more blood relative with breast/ovarian/fallopian tube/primary peritoneal cancer at any age 5) Two primary BC when the first occurrence was prior to age 50 6) Breast cancer with a history of ovarian/ fallopian tube/primary peritoneal cancer at any age 7) For an individual with an ethnicity that is associated with a higher mutation frequency (e.g., Ashkenazi Jewish) 8) Personal history of ovarian/fallopian tube/primary peritoneal cancer 9) Personal history of male breast cancer [38] Solano, 2012 Argentina BRCA1 and BRCA2: All exons and adjacent intronic regions Sequencing 36 23 134 1) diagnosis within 40 years of age and no BOC family history 2) diagnosis at any age with at least two BOC affected 1st or 2nd degree relatives [47] Torres, 2007 Colombia BRCA1 and BRCA2: All exons and adjacent intronic regions SSCP, PTT, DHPLC, sequencing 4 9 44 1)  one female breast cancer diagnosed at or before 35 years of age. 2) two cases of breast cancer diagnosed at any age. 3) three cases of breast cancer with at least one diagnosed at or before 50 years of age. 4) at least four breast cancers with as a minimum one diagnosed at or before 50 years of age. 5) at least one male breast cancer diagnosed at any age. 6) at least one female breast cancer and one or more ovarian cancers at any age [45] Torres, 2009 Colombia BRCA1: del exon 9-12 PCR 0 N/A 229 unselected breast cancer patients, diagnosed at any age [46] Torres-Mejia, 2014 Mexico "BRCA1: exon 10, 5382insC, del exon9-12, 185delAG R1443X, A1708E, C1787S & G1788D, BRCA2: exon 10, 11 W2586X ARMS, CNV, MLPA, PTT, RFLP, sequencing 8 11 810 unselected breast cancer patients, diagnosed at any age [29] Vaca-Paniagua, 2012 Mexico BRCA1 and BRCA2: All exons and adjacent intronic regions Pyrosequencing 13 10 39 1) subjects with breast and/or ovarian cancer and with two or more first- or second-degree relatives with tumors associated with BRCA mutations were studied. 2) male breast cancer. 3) Subjects with early-onset breast cancer 4) subjects with breast and ovarian cancer [19] Vidal-Millan, 2009 Mexico BRCA1 and BRCA2: All exons and adjacent intronic regions PCR, DHPLC, sequencing 8 6 40 1) BC diagnosis at age 40 or younger, with no first or second-degree relatives 2) at least 2 cases of BC and/or OV at any age in first-degree relatives. 3) one case of male BC diagnosed at any age in first-degree relatives. [30] Villarreal-Garza, 2015a Mexico HISPANEL = 115 mutations Sequencing 10 1 190 Patients diagnosed with triple-negative breast cancer at age 50 years or younger. [31] Villarreal-Garza, 2015b Mexico HISPANEL = 114 mutations Pyrosequencing, sequencing, MPLA 8 3 96 unselected breast cancer patients, diagnosed at any age [32] Vogel, 2007 USA-Hispanics BRCA1 and BRCA2: All exons and adjacent intronic regions Myraidb 11 9 95 Subjects had a personal or family history of BC [20] Weitzel, 2013 USA-Hispanics BRCA1 and BRCA2: All exons and adjacent intronic regions Myraidb 11 4 746 Subjects with a personal or family history of BC and/or OV [21]

aNumber of different mutations identified bMutational analysis was done at Myraid Genetic, Inc. Abbreviations: ARMS: Amplification Refractory Mutation System; ASO: Allele-Specific Oligonucleotide Assays; BC: Breast Cancer; CNV: Copy Number Variation Assay; CSGE: Conformation-Specific Gel Electrophoresis; 2DGS: 2-Dimensional Gene Scanning; DHPLC: Denaturing High-Pressure Liquid Chromatography; HDA: Heteroduplex Analyses; MLPA: Multiplex Ligation-Dependent Probe Amplification; OV: Ovarian Cancer; PTT: Protein Truncation Test; RFLP: Restriction Fragment Length Polymorphism; SSCP: Single Strand Conformational Polymorphism

Table 1: Characteristics of included studies.