Background Pathogenicity predictors are integral to genomic variant interpretation but,
despite their widespread usage, an independent validation of performance using a clinically …

Objective Rare genetic disorders resulting in prenatal or neonatal death are genetically
heterogeneous, but testing is often limited by the availability of fetal DNA, leaving couples …

Recent studies have identified both recessive and dominant forms of mitochondrial disease
that result from ATAD3A variants. The recessive form includes subjects with biallelic …

Background The widespread clinical application of genome-wide sequencing has resulted
in many new diagnoses for rare genetic conditions, but testing regularly identifies variants of …

Background ATPase family AAA-domain containing protein 3A (ATAD3A) is a nuclear-encoded
mitochondrial membrane-anchored protein involved in diverse processes including …

Introduction Spermatogenesis is a highly complex process involving several thousand
genes, only a minority of which have been studied in infertile men. In a previous study, we …

Despite the rapid expansion in recent years of databases reporting either benign or pathogenic
genetic variations, the interpretation of novel missense variants remains challenging, …

Mitochondria membrane protein-associated neurodegeneration (MPAN) neurodegenerative
disorder is typically associated with biallelic C19orf12 variants. Here we describe a new …

Purpose We previously defined biallelic HYAL2 variants causing a novel disorder in 2
families, involving orofacial clefting, facial dysmorphism, congenital heart disease, and ocular …

Predicted loss-of-function variants (pLoFs) are often associated with disease. For genes linked
with monogenic diseases, we hypothesised that pLoFs present in apparently unaffected …