Common intronic variant in CACNA1A — the P/Q-type calcium channel gene mutated in familial hemiplegic migraine — that reaches genome-wide significance for migraine with aura; the G (reference) allele confers typical susceptibility while the A allele is mildly protective

Pathogenic glucokinase nonsense variant introducing a premature stop codon that abolishes protein function, causing autosomal dominant maturity-onset diabetes of the young type 2 (MODY2) in heterozygous carriers — the original nonsense mutation in GCK identified in 1992

Rare pathogenic nonsense variant in CYP17A1 causing complete abolition of 17α-hydroxylase/17,20-lyase activity; homozygotes develop the full 17α-hydroxylase deficiency phenotype (hypertension, hypokalemia, absent puberty, low cortisol), while heterozygous carriers are clinically unaffected but carry a CYP17A1 loss-of-function allele relevant to reproductive planning.

Rare pathogenic TTR missense variant causing hereditary transthyretin amyloidosis with predominantly central nervous system and oculoleptomeningeal involvement

Missense variant in the diamine oxidase enzyme that contributes to reduced histamine clearance from dietary sources

No-function CYP2C9 variant with major warfarin implications

Nonsense variant in BMPR2 introducing a premature stop codon (p.Arg321Ter) that truncates the kinase domain; hereditary cause of pulmonary arterial hypertension with incomplete penetrance and autosomal dominant inheritance

Intergenic variant near JAK2 that increases JAK2 expression and JAK-STAT signaling, disrupting intestinal barrier function and increasing IBD susceptibility

Regulatory variant in the lymphotoxin beta receptor gene associated with increased susceptibility to recurrent throat infections and tonsillectomy

PPARG promoter-region enhancer variant that reduces PPARgamma expression, increasing risk for metabolic disease, coronary artery disease, and impaired insulin signalling