It is possible to estimate the prior probability of pathogenicity for germline disease gene
variants based on bioinformatic prediction of variant effect/s. However, routinely used …

Once called “silent mutations” and assumed to have no effect on protein structure and
function, synonymous variants are now recognized to be drivers for some cancers. There …

Germline variants in tumor suppressor genes (TSGs) can result in RNA mis-splicing and
predisposition to cancer. However, identification of variants that impact splicing remains a …

Many individuals with muscular dystrophies remain genetically undiagnosed despite clinical
diagnostic testing, including exome sequencing. Some may harbor previously undetected …

Mutations that perturb normal pre-mRNA splicing are significant contributors to human
disease. We used exome sequencing data from 7833 probands with developmental …

Simple Summary Colorectal cancer (CRC) in adolescents and young adults (AYA) is rare.
Genetic causes include autosomal recessive and dominant monogenic disorders due to …

Background Disrupted pre-mRNA splicing is a frequent deleterious mechanism in hereditary
cancer. We aimed to functionally analyze candidate spliceogenic variants of the breast …

Mutation screening of the breast cancer genes BRCA1 and BRCA2 identifies a large fraction
of variants of uncertain clinical significance (VUS) whose functional and clinical …

Monoallelic PMS2 germline mutations cause 5%–15% of Lynch syndrome, a midlife cancer
predisposition, whereas biallelic PMS2 mutations cause approximately 60% of constitutional …

Background Variants that disrupt mRNA splicing account for a sizable fraction of the
pathogenic burden in many genetic disorders, but identifying splice-disruptive variants …