Chloe M. Reuter

MetaDome 2027: a comprehensively updated resource for aggregating missense variant evidence across homologous human protein domains

MetaDome now supports GRCh38 alongside GRCh37, adds coordinate lookup, and identifies 52,463 GRCh38 ClinVar missense variants of uncertain significance with uncontradicted pathogenic evidence at homologous Pfam-domain positions.

Cardiovascular genetic counseling is associated with improved patient-reported outcomes across clinical indications and settings

This study shows cardiovascular genetic counseling improves patient empowerment and reduces worry, with benefits varying by patient characteristics and the strength of the counselor-patient relationship.

Damaging RBM20 E-rich domain variants are not rescued by gene replacement

The paper investigates E-rich domain variants of RBM20, showing they reduce protein abundance and cause splicing defects, but are not rescued by RBM20 overexpression.

Ensilication preserves high-molecular weight native DNA for clinical long-read sequencing

This paper demonstrates that ensilication preserves DNA integrity at ambient temperature, enabling diagnostic-quality long-read sequencing without cold-chain infrastructure.

Population-scale detection of methylation outliers from long-read genome sequencing

METAFORA calls depth-aware, covariate-adjusted methylation outlier regions from PacBio and Nanopore long reads; in 551 rare-disease genomes, outliers tracked structural variants, repeat expansions, and imprinting defects.

An optimized variant prioritization process for rare disease diagnostics: recommendations for Exomiser and Genomiser

This paper optimizes variant prioritization parameters for Exomiser and Genomiser to improve diagnostic yield in rare disease cases using WES and WGS data.

Biallelic variants in the non-coding RNA gene RNU4-2 cause a recessive neurodevelopmental syndrome with distinct white matter changes

The paper identifies biallelic variants in RNU4-2 causing a recessive neurodevelopmental syndrome with distinct white matter changes, expanding the known genotypic and phenotypic spectrum of RNU4-2-related disorders.

Clinical Validity of Autosomal Dominant ALPK3 Loss-of-function Variants as a Cause of Hypertrophic Cardiomyopathy

The paper evaluates the clinical validity of heterozygous ALPK3 loss-of-function variants as a cause of hypertrophic cardiomyopathy, finding strong gene-disease association with reduced penetrance.

Integration of transcriptomics and long-read genomics prioritizes structural variants in rare disease

The paper integrates long-read sequencing and gene expression to prioritize functional structural variants and tandem repeats in rare disease patients, identifying potential causal variants in a neurodevelopmental disorder.

Population-scale variability at short tandem repeat loci reveals pathogenicity signature

The paper uses long-read sequencing data to analyze STR variability across 2,645 individuals, identifying disease-associated STR loci with elevated allelic variability and introducing the PLVI metric.

De novo variants in the non-coding spliceosomal snRNA gene RNU4-2 are a frequent cause of syndromic neurodevelopmental disorders

Mostly de novo variants in an 18 bp constrained region of U4 snRNA gene RNU4-2 cause a syndromic neurodevelopmental disorder, estimated to explain 0.41% of cases.

Researcher Views on Multi-omics Return of Results to Research Participants: Insights from the Molecular Transducers of Physical Activity Consortium (MoTrPAC) Study

The paper explores researchers' perspectives on returning multi-omics results to participants in the MoTrPAC study, highlighting both support and concerns about ethical, logistical, and communication challenges.

Clinical application of Complete Long Read genome sequencing identifies a 16kb intragenic duplication in EHMT1 in a patient with suspected Kleefstra syndrome

The paper applies complete long read sequencing to undiagnosed patients, identifying a 16kb intragenic duplication in EHMT1 causing Kleefstra syndrome.

RExPRT: a machine learning tool to predict pathogenicity of tandem repeat loci

RExPRT predicts pathogenicity of tandem repeat expansions with high precision, identifying ~30,000 likely pathogenic TRs in the reference genome.

De novo EIF2AK1 and EIF2AK2 variants are associated with developmental delay, leukoencephalopathy, and neurologic decompensation

The paper identifies de novo variants in EIF2AK1 and EIF2AK2 associated with neurodevelopmental disorders and leukoencephalopathy, showing similar pathogenic mechanisms to CACH/VWM.