Allele

One of two or more versions of a DNA sequence at a given genomic location. Different alleles may lead to different traits or disease susceptibility.

Autosomal Dominant

A pattern of inheritance in which a single copy of a pathogenic variant on a non-sex chromosome is sufficient to cause disease. Each child of an affected parent has a 50% chance of inheriting the variant.

Autosomal Recessive

A pattern of inheritance requiring two copies of a pathogenic variant (one from each parent) to manifest disease. Carrier parents have a 25% chance of having an affected child with each pregnancy.

De Novo Variant

A genetic alteration present in a child but not found in either parent, arising spontaneously during germ cell formation or very early embryonic development.

Exome Sequencing

A laboratory method that sequences the protein-coding regions of the genome (approximately 1–2% of total DNA), where roughly 85% of known disease-causing variants reside.

Genotype

The genetic constitution of an individual at one or more specific loci, as opposed to the observable physical characteristics (phenotype).

Loss of Function (LoF)

A variant that abolishes or significantly reduces normal gene product activity, often through premature stop codons, frameshift insertions/deletions, or splice-site disruption.

Missense Variant

A single nucleotide change resulting in incorporation of a different amino acid into the protein. The clinical significance depends on the amino acid change, protein domain, and functional consequences.

Pathogenic Variant

A DNA sequence change classified as disease-causing according to ACMG/AMP guidelines, based on population data, computational predictions, functional studies, and segregation analysis.

Penetrance

The proportion of individuals carrying a specific pathogenic variant who develop clinical features of the associated condition. Reduced penetrance complicates genetic counseling and risk assessment.

Phenotype

The observable clinical characteristics of an individual—including physical features, biochemical traits, and disease manifestations—resulting from the interaction of genotype with environment.

Proband

The individual in a family who first comes to medical attention and through whom the family is ascertained for genetic evaluation and possible testing.

Variant of Uncertain Significance (VUS)

A DNA sequence change that cannot be definitively classified as pathogenic or benign based on currently available evidence. VUS rates vary by gene and population.

Whole Genome Sequencing (WGS)

A comprehensive laboratory method that determines the complete DNA sequence of an organism, including protein-coding, regulatory, and non-coding regions.

X-Linked Inheritance

A pattern of inheritance for genes located on the X chromosome. X-linked recessive conditions predominantly affect males, while females may be carriers with variable expression due to X-inactivation.

Glossary