Summary of germline <i>RAD51D</i> variants.

a<p>Exon (Ex), intervening sequence (IVS).</p>b<p>Variant positions are reported in reference to NCBI RefSeq NM_002878.3 (mRNA) and NP_002869 (protein).</p>c<p>In addition to the variants listed, common variants rs4796033, rs28363284 (non-synonymous) and rs9901455 (synonymous) were detected at high frequency in both cases and controls.</p>d<p>All variants were queried against 1000 Genomes (1000 G) data using the 1000 Genomes Browser which integrates SNP and indel calls from 1,092 individuals (data release 20110521 v3). The minor allele frequency (MAF) is provided here.</p>e<p>All variants were queried against Exome Variant Server (EVS), NHLBI Exome Sequencing Project (ESP). EVS contains SNP information from 5,379 individuals (data release ESP5400). The minor allele frequency (MAF) is provided here.</p>f<p>Breast cancer only family (BC), ovarian cancer only family (OC), breast and ovarian cancer family (BC/OC).</p>g<p>Variants annotated with N/A were not assessed in control samples.</p>h<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0054772#pone.0054772-Grantham1" target="_blank">[22]</a>.</p

Loss of heterozygosity analysis of the c.556C>T (p.(Arg186*)) variant.

<p>Sequencing (forward and reverse) of the heterozygous c.556C>T variant in the germline sample, and tumour DNA showing loss of the wildtype allele (with some contamination from normal DNA).</p

Primers used for mutation analysis of <i>RAD51D</i>.

<p>Primers used for mutation analysis of <i>RAD51D</i>.</p

Characteristics of 15 high-risk breast cancer families selected for exome sequencing.

a<p>Breast cancer (BC), ovarian cancer (OC), bilat. (bilateral). Age of diagnosis shown in parentheses.</p>b<p>Other cancer types observed in family branch with apparent breast cancer risk (multiple cases shown in parentheses).</p

<i>FANCC</i> and <i>BLM</i> mutations identified in familial breast cancer pedigrees.

<p>Males and females are represented by squares and circles, respectively. Arrows indicate individuals who underwent whole exome sequencing (families 1–3) or were the index case in subsequent mutation analysis (<i>FANCC</i> p.Asp23fs, p.Leu554Pro and p.Arg185Gln and <i>BLM</i> p.Arg899* families). Cancer-affected individuals are represented with the following symbols: breast cancer, top right quadrant filled in; bilateral breast cancer, top half; ovarian cancer, bottom left quadrant; or other cancers as indicated, centre circle. Mutation status is indicated with either the family specific mutation or wildtype (wt) under each tested individual. Age at cancer diagnosis or year of birth (b.) where known is shown for all mutation carriers. Breast cancer (BC), ovarian cancer (OC), acute leukaemia (AL), colorectal cancer (CRC), haematological malignancy (type unspecified) (Haem.), kidney cancer (KC), liver cancer (LivC), melanoma (Mel.), pancreatic cancer (PaC), prostate cancer (PrC), skin non-melanoma (Non-mel.) stomach cancer (SC), testicular cancer (TestC). Mutations indicated in parentheses indicate untested obligate carriers. Family 2 contains an individual (indicated by #) for whom mutation status is inferred assuming that non-paternity or gonadal mosaicism have not occurred.</p

The TREVA workflow: execution of primary and secondary pipelines for variant calling on individual and related groups of samples.

<p>The TREVA workflow: execution of primary and secondary pipelines for variant calling on individual and related groups of samples.</p

Primary analysis pipelines.

<p>Red colour highlights the difference between our Somatic Pipeline and Familial (Germline) Pipeline.</p