Where genotype is not predictive of phenotype: towards an understanding of the molecular basis of reduced penetrance in human inherited disease

DN Cooper, M Krawczak, C Polychronakos… - Human genetics, 2013 - Springer
Some individuals with a particular disease-causing mutation or genotype fail to express
most if not all features of the disease in question, a phenomenon that is known as 'reduced …

[HTML][HTML] BRCA1-and BRCA2-associated hereditary breast and ovarian cancer

N Petrucelli, MB Daly, T Pal - 2022 - europepmc.org
BRCA1-and BRCA2-associated hereditary breast and ovarian cancer (HBOC) is
characterized by an increased risk for female and male breast cancer, ovarian cancer …

Accurate classification of BRCA1 variants with saturation genome editing

GM Findlay, RM Daza, B Martin, MD Zhang, AP Leith… - Nature, 2018 - nature.com
Variants of uncertain significance fundamentally limit the clinical utility of genetic information.
The challenge they pose is epitomized by BRCA1, a tumour suppressor gene in which …

Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer

FJ Couch, SN Hart, P Sharma, AE Toland… - Journal of clinical …, 2015 - ascopubs.org
Purpose Recent advances in DNA sequencing have led to the development of breast cancer
susceptibility gene panels for germline genetic testing of patients. We assessed the …

BRCA Challenge: BRCA Exchange as a global resource for variants in BRCA1 and BRCA2

MS Cline, RG Liao, MT Parsons, B Paten… - PLoS …, 2018 - journals.plos.org
The BRCA Challenge is a long-term data-sharing project initiated within the Global Alliance
for Genomics and Health (GA4GH) to aggregate BRCA1 and BRCA2 data to support highly …

Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database

BA Thompson, AB Spurdle, JP Plazzer, MS Greenblatt… - Nature …, 2014 - nature.com
The clinical classification of hereditary sequence variants identified in disease-related genes
directly affects clinical management of patients and their relatives. The International Society …

Two Decades After BRCA: Setting Paradigms in Personalized Cancer Care and Prevention

FJ Couch, KL Nathanson, K Offit - Science, 2014 - science.org
The cloning of the breast cancer susceptibility genes BRCA1 and BRCA2 nearly two
decades ago helped set in motion an avalanche of research exploring how genomic …

Identifying breast cancer susceptibility genes–a review of the genetic background in familial breast cancer

C Wendt, S Margolin - Acta Oncologica, 2019 - Taylor & Francis
Introduction: Heritage is the most important risk factor for breast cancer. About 15–20% of
breast cancer is familial, referring to affected women who have one or more first-or second …

Biallelic Mutations in BRCA1 Cause a New Fanconi Anemia Subtype

SL Sawyer, L Tian, M Kähkönen… - Cancer …, 2015 - aacrjournals.org
Deficiency in BRCA-dependent DNA interstrand crosslink (ICL) repair is intimately
connected to breast cancer susceptibility and to the rare developmental syndrome Fanconi …

[HTML][HTML] Massively parallel functional testing of MSH2 missense variants conferring Lynch syndrome risk

X Jia, BB Burugula, V Chen, RM Lemons… - The American Journal of …, 2021 - cell.com
The lack of functional evidence for the majority of missense variants limits their clinical
interpretability and poses a key barrier to the broad utility of carrier screening. In Lynch …