Marina T. DiStefano

The paper surveys genetics professionals on their use of functional evidence in variant classification for hearing and vision loss, highlighting challenges in data quality, accessibility, and integration into clinical practice.

PFES quantifies the protein context of missense variants, enabling mechanistically transparent interpretation and reclassification of variants of uncertain significance.

The paper describes international workshops training variant scientists on the ClinGen Variant Curation Interface (VCI) and reports on its usage and costs.

This study uses long-read sequencing to characterize MUC1 VNTR variation in ADTKD-MUC1, identifying frameshift mutations and their association with disease progression.

The paper curates 111 gene-disease relationships for syndromic disorders, classifying their clinical validity and identifying gaps in knowledge.

This paper standardizes terminology for describing disease-gene relationships to improve variant classification and genetic test interpretation.

The paper describes the formation of the Gene Curation Coalition to standardize gene-disease validity terminology and create a unified database for curated gene-disease assertions.

The paper introduces the ClinGen Variant Curation Interface, a platform for applying ACMG/AMP guidelines to classify genetic variants, enabling collaboration and standardization in clinical variant interpretation.

The paper curates 157 variants in hearing loss genes using disease-specific ACMG/AMP guidelines, resolving 69% of discordant variants and 24% of VUS variants into clear classifications.

The paper resolves the classification of two GJB2 variants as pathogenic for autosomal recessive nonsyndromic hearing loss through expert consensus.

The paper curates 164 gene-disease pairs for hearing loss, classifying their clinical validity to improve genetic testing accuracy.

The paper specifies ACMG/AMP variant interpretation guidelines for genetic hearing loss, updating and validating rules through expert curation of 51 variants.

The paper provides refined recommendations for applying the PVS1 ACMG/AMP variant criteria to loss of function variants, addressing gaps in the original guideline through evaluation with curated variants.

The paper curates clinically relevant transcripts for 109 hearing loss-associated genes to improve variant interpretation by classifying exons based on expression, variant frequency, and sequencing quality.

The paper presents a framework to evaluate the clinical validity of gene-disease associations, validated using representative gene-disease pairs.