3'UTR variant that alters miR-150 binding affinity; the C allele increases microRNA-mediated suppression of MTOR expression and is associated with improved cancer prognosis and reduced mTOR pathway activity

Pathogenic missense variant in ALK1 kinase domain causing hereditary hemorrhagic telangiectasia type 2 (HHT2) and pulmonary arterial hypertension

Pathogenic LDLR missense variant (p.Tyr828Cys) that traps LDL receptors outside coated pits, causing familial hypercholesterolemia with severely elevated LDL-C and early-onset cardiovascular disease

Nonsense mutation in argininosuccinate lyase introducing a premature stop codon that abolishes the fourth step of the urea cycle; a founder allele in Arab populations causing argininosuccinic aciduria, the second most common urea cycle disorder — homozygotes develop neonatal hyperammonemia and require lifelong arginine supplementation, protein restriction, and hepatic surveillance

Promoter variant that disrupts an SP1 transcription factor binding site, increasing MMP-9 expression in vascular tissue; the T allele is associated with elevated plaque instability, higher risk of myocardial infarction, and increased ischemic stroke risk, particularly in Asian populations

Pathogenic missense variant in biotinidase that abolishes biotin recycling; heterozygous carriers have partial enzyme reduction while homozygotes and compound heterozygotes develop biotinidase deficiency requiring lifelong biotin supplementation

Splice donor variant disrupting DNAI1 intron 19, causing in-frame deletion of exon 19 (A607_K667del); pathogenic for autosomal recessive primary ciliary dyskinesia with outer dynein arm defects, chronic sinopulmonary disease, and situs inversus

Rare pathogenic/likely pathogenic missense variant in the C5 immunoglobulin-like domain of cardiac myosin-binding protein C, disrupting sarcomere assembly and causing hypertrophic cardiomyopathy through haploinsufficiency (autosomal dominant)

Gain-of-function missense variant in the CARD9 adaptor protein that enhances antifungal immune signaling, increasing susceptibility to inflammatory bowel disease, allergic bronchopulmonary aspergillosis, and recurrent fungal infections

Intronic glucocorticoid receptor variant affecting cortisol sensitivity and stress response regulation