Splice-site variants in neurology: from molecular mechanisms to clinical interpretation — a focused review

Natural Missplicing Events Amplified by an Elusive Deep-Intronic MYBPC3 Variant Cause Hypertrophic Cardiomyopathy.

BACKGROUND Disruption of MYBPC3 precursor mRNA splicing is a frequent genetic cause of hypertrophic cardiomyopathy (HCM). Most often, it reflects changes at canonical sites or the creation of novel splice sites. Prediction tools usually prioritize splice variants with lower efficiency when they are distant from canonic...

Improving molecular diagnosis of fabry disease: functional validation of novel splicing variants in GLA

The findings highlight the critical role of robust functional splicing assays in interpreting variant pathogenicity, establishing accurate genotype-phenotype correlations, and ultimately facilitating precision medicine for FD.

Genome sequencing reveals novel pathogenic deep-intronic PCDH15 variants, amenable to antisense oligonucleotide-based splice correction

Mapping intronic mutational hotspots by in silico mutagenesis enables single antisense oligonucleotide correction of multiple variants

This gene-agnostic framework establishes a systematic strategy for identifying intronic mutational hotspots and matching patients to scalable, mutation-agnostic ASO-based precision therapies.

Rapid minigene workflow for functional reclassification of splicing variants in hereditary cancer diagnostics

A streamlined minigene-based workflow for rapid functional evaluation of splicing variants and a robust and scalable framework for functional interpretation of splicing variants is developed, improving diagnostic resolution and supporting more informed clinical decision-making in hereditary cancer genetics.

Functional Validation of a Novel Homozygous TTN Splice‐Site Variant Reveals Aberrant Splicing in Hypertrophic Cardiomyopathy

The TTN gene encodes a crucial structural protein within cardiac sarcomeres, and its variants may contribute to hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy; however, phenotype and genotype are different. Whole‐exome sequencing (WES) was conducted on a Chinese proband diagnosed with HCM. In silico splic...