Next-generation sequencing has revolutionized clinical diagnostic testing. Yet, for a
substantial proportion of patients, sequence information restricted to exons and exon–intron …

Genetic abnormalities in the DNA repair genes BRCA1 and BRCA2 predispose to hereditary
breast and ovarian cancer (HBOC). However, only approximately 25% of cases of HBOC …

Public health newborn screening (NBS) programs provide population-scale ascertainment
of rare, treatable conditions that require urgent intervention. Tandem mass spectrometry …

In silico tools have been developed to predict variants that may have an impact on pre-
mRNA splicing. The major limitation of the application of these tools to basic research and …

In metazoans, alternative splicing of genes is essential for regulating gene expression and
contributing to functional complexity. Computational predictions, comparative genomics, and …

The lack of tools to identify causative variants from sequencing data greatly limits the
promise of precision medicine. Previous studies suggest that one-third of disease …

We present an intuitive strategy for predicting the effect of sequence variation on splicing. In
contrast to transcriptional elements, splicing elements appear to be strongly position …

The identification of a causal mutation is essential for molecular diagnosis and clinical
management of many genetic disorders. However, even if next-generation exome …

Abstract The Human Gene Mutation Database (HGMD) constitutes a comprehensive core
collection of data on germ‐line mutations in nuclear genes underlying or associated with …

The removal by splicing of introns from the primary transcripts of most mammalian genes is
an essential step in gene expression. Splicing is performed by large, complex …