Gene Notation: Genotype Symbols, Alleles and HGVS Variants

Gene notation is a set of layered conventions, not one system. Letter pairs such as BB, Bb and bb write a genotype; capitalisation and italics separate a gene symbol from its protein, and differ between human and mouse nomenclature; superscripts name mouse alleles; and HGVS strings such as c.4375C>T describe a specific sequence variant. Reading a symbol correctly starts with knowing which layer it belongs to.

Definition and scope

This guide covers four notation layers that are often blurred together under “genetic notation”: genotype letter pairs, gene and protein symbols, allele symbols, and variant descriptions. Each has its own authority. The NHGRI genetics glossary defines the genotype letters, the HUGO Gene Nomenclature Committee (HGNC) sets human gene symbols, the Mouse Genome Informatics (MGI) database sets mouse gene and allele symbols, and the Human Genome Variation Society (HGVS) sets the format for sequence variants. For the wider field, see what molecular biology covers and what genomics covers.

Genotype symbols: what BB, Bb, bb and tt mean

NHGRI defines a genotype as “a scoring of the type of variant present at a given location (i.e., a locus) in the genome,” and notes that it can be represented by symbols, for example BB, Bb and bb. A genotype can equally be written as bases, such as CC, CT and TT.

What does the notation tt mean in genetics?

tt is a two-letter genotype at one locus. By the common textbook convention, two identical letters mean the same allele is present on both chromosomes, and a lowercase letter marks the recessive allele, so tt is the genotype of an individual carrying two copies of the recessive allele. That lowercase-recessive reading is a convention of teaching examples, not a universal rule: the sections below show that gene and allele nomenclatures follow their own rules.

The same convention explains why BB, Bb and bb are the three possible genotypes for one gene with two alleles. For a worked use of letter-pair genotypes across two genes at once, see the dihybrid cross guide.

Gene symbols versus protein symbols

Gene symbols follow species-specific rules. Two of the best-documented are the human and mouse systems.

• Human (HGNC): symbols contain only uppercase Latin letters and Arabic numerals, and punctuation is avoided, with an exception for hyphens in specific groups. HGNC distinguishes proteins from genes by writing protein symbols without italics.
• Mouse (MGI): a gene symbol begins with an uppercase letter, followed by lowercase letters or numbers, normally three to five characters and not more than ten, for example Glra1. Genes known only by a recessive mutant phenotype begin with a lowercase letter, while symbols from dominant or semidominant phenotypes begin uppercase. MGI states that you should never prepend “m” to a mouse gene symbol or “r” to a rat gene symbol, and that gene symbols are italicised when published.

The practical consequence is that capitalisation carries information. A symbol in all capitals with numerals is the human convention; an initial capital followed by lowercase is the mouse convention. Always check which species a paper is writing about before inferring anything from case.

Allele notation: reading superscripts

MGI writes an allele by adding the mutant allele symbol as a superscript to the gene symbol. The superscript keeps its own initial upper or lower case, and allele symbols are italicised along with gene symbols. MGI’s own examples show how to read them:

• Grid2^ho is an allele of the Grid2 gene.
• Kit^W-v is an allele of the Kit gene, with hyphenated allele text.
• tp^2J is the second new allele of the taupe gene identified at The Jackson Laboratory. The gene symbol begins lowercase because taupe is known from a recessive mutant phenotype.

So allele notation answers a different question from genotype notation. BB, Bb and bb say which alleles an individual carries at a locus; a superscript says which named allele of a gene is meant.

HGVS variant notation

When a paper or database needs to name an exact change in sequence, it uses HGVS nomenclature. HGNC states that sequence variant nomenclature is the remit of HGVS, so gene-symbol rules do not cover it. A description follows the pattern prefix, position, change. The prefix says what kind of reference sequence the position counts along:

• c. coding DNA
• g. genomic
• r. RNA
• p. protein

In the HGVS example c.4375C>T, the base C at position 4375 is changed to T, with “>” marking a substitution. A full description names the reference first, as in NM_004006.3:c.4375C>T, or at genomic level NC_000023.11:g.32389644G>A. HGVS’s own examples show gene symbols such as DMD in italics and variant descriptions in code font. Parentheses mean the consequence is predicted rather than observed, so p.(Arg1459Ter) is a predicted protein consequence. Tools that report variants in files follow the same logic; see reading a VCF file and the dbSNP entry.

Four layers compared

Layer	Example	What it tells you	Authority
Genotype letters	BB, Bb, bb; CC, CT, TT	The variants present at a locus	NHGRI genetics glossary
Human gene symbol	Uppercase letters and numerals; protein not italic	Which human gene, or its protein	HGNC guidelines
Mouse gene and allele symbol	Glra1; KitW-v	Which mouse gene, and which named allele	MGI nomenclature
Sequence variant	NM_004006.3:c.4375C>T	An exact change on a stated reference	HGVS

Where it matters for labs and clinics

Notation errors travel into methods sections, genotyping sheets and database submissions. Three checks catch most of them: confirm the species before reading a symbol’s capitalisation; separate the gene (italic) from the protein it encodes (not italic in HGNC practice); and, for variants, always state the reference sequence version alongside the c. or g. position, because HGVS positions are meaningful only against a named reference. For the reference records behind those identifiers, see NCBI RefSeq. For conditional alleles built in the mouse, see Cre-lox conditional knockout lines.

Common misunderstandings

• “Lowercase always means recessive.” In genotype teaching examples it often does, but in MGI nomenclature a lowercase initial can mean the symbol comes from a recessive mutant phenotype, which is a statement about the gene symbol, not about a letter pair.
• “A human symbol and a mouse symbol are interchangeable.” MGI explicitly forbids prefixing mouse symbols with “m”; case follows each species’ own rules.
• “c. and p. are interchangeable.” They count positions along different sequences (coding DNA versus protein).
• “Parentheses are decoration.” In HGVS they mean the consequence is predicted only.

FAQ

What does the notation tt mean in genetics?

It is a two-letter genotype at one locus. Under the usual convention, identical letters mean the same allele on both chromosomes and lowercase marks a recessive allele, so tt means two copies of the recessive allele.

What are genotype symbols?

Letters that record which variants an individual has at a locus. NHGRI gives BB, Bb and bb as examples, and notes that genotypes can also be written as bases such as CC, CT and TT.

What is allele notation?

A way of naming a specific allele of a gene. In mouse nomenclature (MGI) the allele symbol is added as a superscript to the gene symbol, for example Kit^W-v, and both are italicised in publication.

Sources

• NHGRI, Talking Glossary of Genomic and Genetic Terms, “Genotype”: https://www.genome.gov/genetics-glossary/Genotype (checked 2026-10-29).
• HUGO Gene Nomenclature Committee, guidelines: https://www.genenames.org/about/guidelines/ (checked 2026-10-29).
• Mouse Genome Informatics, Guidelines for Nomenclature of Genes, Genetic Markers, Alleles, and Mutations in Mouse and Rat, section 2.3.1: https://www.informatics.jax.org/mgihome/nomen/gene.shtml (checked 2026-10-29).
• HGVS Nomenclature, simple variant background: https://hgvs-nomenclature.org/stable/background/simple/ (checked 2026-10-29).