Variant

Variant is an alteration in the most common DNA nucleotide sequence. Variants are defined based on the type of DNA error (see table below). The term variant can be used to describe an alteration that may be benign, pathogenic, or of unknown significance. Variants may be germline or somatic.
*The term variant is increasingly being used in place of the term mutation.3

Deletion

Deletion is a type of variant involving the loss of genetic material. It can be small, involving a single missing DNA base pair, or large, involving a piece of a chromosome.4
Example: Original DNA Sequence: the gray cat ran down the hall; Deletion Sequence: the gray ___ ran down the hall
Deletion Illustration

Duplication

Duplication is a type of variant that involves the production of one or more copies of a gene or region of a chromosome. Gene and chromosome duplications occur in all organisms, though they are especially prominent among plants. Gene duplication is an important mechanism by which evolution occur.4
Example: Original DNA Sequence: the gray cat ran down the hall; Duplication Sequence: the gray cat cat ran down the hall
Duplication Illustration

Frameshift

A frameshift variant is a type of variant involving the insertion or deletion of a nucleotide in which the number of deleted base pairs is not divisible by three. "Divisible by three" is important because the cell reads a gene in groups of three bases. Each group of three bases corresponds to one of 20 different amino acids used to build a protein. If a mutation disrupts this reading frame, then the entire DNA sequence following the mutation will be read incorrectly.4
Example: Original DNA Sequence: the gray cat ran down the hall; Frameshift insertion: thh egra yca tra ndow nth ehal l; Frameshift deletion: the rayc atr and ownt heh all
Frameshift Illustration

Insertion

Insertion is a type of variant involving the addition of genetic material. An insertion variant can be small, involving a single extra DNA base pair, or large, involving a piece of a chromosome.4
Example: Original DNA Sequence: the gray cat ran down the hall; Insertion Sequence: the gray red cat ran down the hall
Insertion Illustration

Large Genomic Rearrangements

Large genomic rearrangements are large deletions or insertions of DNA (i.e. an exon deleted) as well as structural changes such as translocations or inversions.13 
Example: Original DNA Sequence: the gray cat ran down the hall; Large Genomic Rearrangement Sequence: the
Large genomic rearrangements make up approximately 12-18% of variants found in BRCA1.13

Microsatellite Instability (MSI)

A characteristic of cells that contain an abnormality in DNA mismatch repair (see microsatellite).3
Clinical Example: The presence of MSI in colorectal tumor tissue may be used as a marker for germline mutations in one of the DNA mismatch repair genes associated with Lynch Syndrome. MSI can also occur sporadically, and in these cases is related to gene hypermethylation.3

Missense

A characteristic of cells that contain an abnormality in DNA mismatch repair (see microsatellite).3
Example: Original DNA Sequence: the gray cat ran down the hall; Missense Sequence: the grey cat ran down the hall
Missense Illustration

Nonsense

A nonsense variant is the substitution of a single base pair that leads to the appearance of a stop codon where previously there was a codon specifying an amino acid. The presence of this premature stop codon results in the production of a shortened, and likely nonfunctional, protein.4
Example: Original DNA Sequence: the gray cat ran down the hall; Nonsense Sequence: the gray
Nonsense Illustration

Polymorphism

A variant with a frequency in the general population of greater than 1%.8
Example: Many variants associated with drug metabolism (pharmacogenomics) are polymorphisms.

Single Nucleotide Polymorphism (SNP)

DNA sequence variations that occur when a single nucleotide (adenine, thymine, cytosine, or guanine) in the genome sequence is altered; usually present in at least 1% of the population.3
Single Nucleotide Polymorphism Illustration

Substitution

A substitution is a type of variant where one base pair is replaced by a different base pair. The term also refers to the replacement of one amino acid in a protein with a different amino acid.4
Substitution Illustration