TY - JOUR AU - Brookes, Clare AU - Lai, Stella AU - Doherty, Elaine AU - Love, Donald R. PY - 2015/05/01 Y2 - 2024/03/29 TI - Predicting the Pathogenic Potential of BRCA1 and BRCA2 Gene Variants Identified in Clinical Genetic Testing JF - Sultan Qaboos University Medical Journal JA - Sultan Qaboos Univ Med J VL - 15 IS - 2 SE - Original Studies DO - UR - https://journals.squ.edu.om/index.php/squmj/article/view/2019 SP - 218-225 AB - <span><span>Objectives:</span></span><span> Missense variants are very commonly detected when screening for mutations in the</span><span> BRCA1</span><span> and </span><span>BRCA2</span><span> genes. Pathogenic mutations in the </span><span>BRCA1</span><span> and </span><span>BRCA2</span><span> genes lead to an increased risk of developing breast, ovarian, prostate and/or pancreatic cancer. This study aimed to assess the predictive capability of </span><span>in silico</span><span> programmes and mutation databases in assisting diagnostic laboratories to determine the pathogenicity of sequence-detectable mutations. </span><span><span>Methods:</span></span><span> Between July 2011 and April 2013, an analysis was undertaken of 13 missense </span><span>BRCA</span><span> gene variants that had been detected in patients referred to the Genetic Health Services New Zealand (Northern Hub) for </span><span>BRCA</span><span> gene analysis. The analysis involved the use of 13 </span><span>in silico</span><span> protein prediction programmes, two </span><span>in silico</span><span> transcript analysis programmes and the examination of three </span><span>BRCA</span><span> gene databases.</span><span><span> Results:</span></span><span> In most of the variants, the analysis showed different in silico interpretations. This illustrates the interpretation challenges faced by diagnostic laboratories. </span><span><span>Conclusion:</span></span><span> Unfortunately, when using online mutation databases and carrying out </span><span>in silico</span><span> analyses, there is significant discordance in the classification of some missense variants in the </span><span>BRCA</span><span> genes. This discordance leads to complexities in interpreting and reporting these variants in a clinical context. The authors have developed a simple procedure for analysing variants; however, those of unknown significance largely remain unknown. As a consequence, the clinical value of some reports may be negligible.</span><br /><span><span><br /><br /></span></span> ER -