Human Mutation,

TAB2 c.1398dup variant leads to haploinsufficiency and impairs extracellular matrix homeostasis

Abstract Transforming growth factor β‐activated kinase 1 (TAK1) mediates multiple biological processes through the nuclear factor κ‐light‐chain‐enhancer of activated B cells (NF‐κB) and the mitogen‐activated protein kinase (MAPK) signaling pathways. TAK1 activation is tightly regulated by its binding partners (TABs). In particular, binding with TAB2 is crucial for cardiovascular development and extracellular matrix (ECM) homeostasis. In our previous work, we reported a novel multisystem disorder...

Human Mutation

Thu Jun 27, 2019 20:53

Contribution to colonic polyposis of recently proposed predisposing genes and assessment of the prevalence of NTHL1‐ and MSH3‐associated polyposes

ABSTRACT Technological advances have allowed the identification of new adenomatous and serrated polyposis genes, and of several candidate genes that require additional supporting evidence of causality. Through an exhaustive literature review and mutational screening of 177 unrelated polyposis patients, we assessed the involvement of MCM9, FOCAD, POLQ and RNF43 in the predisposition to (non‐serrated) colonic polyposis, as well as the prevalence of NTHL1 and MSH3 mutations among genetically unexplained...

Human Mutation

Thu Jun 27, 2019 11:58

Predicting changes in protein stability caused by mutation using sequence‐ and structure‐based methods in a CAGI5 blind challenge

Abstract Predicting the impact of mutations on proteins remains an important problem. As part of the CAGI5 frataxin challenge, we evaluate the accuracy with which Provean, FoldX, and ELASPIC can predict changes in the Gibbs free energy of a protein using a limited data set of eight mutations. We find that different methods have distinct strengths and limitations, with no method being strictly superior to other methods on all metrics. ELASPIC achieves the highest accuracy while also providing a web...

Human Mutation

Thu Jun 27, 2019 11:58

Assessing the performance of in‐silico methods for predicting the pathogenicity of variants in the gene CHEK2, among Hispanic females with breast cancer

Abstract The availability of disease‐specific genomic data is critical for developing new computational methods that predict the pathogenicity of human variants and advance the field of precision medicine. However, the lack of gold standards to properly train and benchmark such methods is one of the greatest challenges in the field. In response to this challenge, the scientific community is invited to participate in the Critical Assessment for Genome Interpretation (CAGI), where unpublished disease...

Human Mutation

Wed Jun 26, 2019 12:03