Introduction to HGVS Nomenclature

The Human Genome Variation Society (HGVS) nomenclature provides a systematic approach for describing sequence variants in DNA, RNA, and proteins. This standardized system, authorized by the Human Genome Organization (HUGO), is essential for accurate, unambiguous, and stable reporting of genetic variations. It plays a critical role in clinical diagnostics and research, particularly in understanding diseases and drug responses.

Components of HGVS Nomenclature

1. Reference Sequence
Every variant description begins with a reference sequence, which is identified by a two-letter abbreviation, a multi-digit number, and a version number. This sequence serves as the baseline for identifying variants.

2. Variant Description
The description of the variant follows the reference sequence. It varies depending on the type of variant (SNVs, indels, etc.) and the level (DNA, RNA, protein) at which the variant occurs.

3. Predicted Consequence
The description concludes with the predicted consequence of the variant, enclosed in parentheses. This provides insight into the potential impact of the variant on the organism.

Types of Nomenclature

a. c. Nomenclature (DNA Level)
Focus: Single nucleotide variants (SNVs)
Format: "c.[position]C>T" (e.g., "NM_004006.2:c.4375C>T")
Usage: Widely used in describing single nucleotide polymorphisms (SNPs), the most common type of genetic variation.

b. g. Nomenclature (Genomic Level)
Format: "g.[position]C>T" (e.g., "NC_000023.11:g.32407761G>A")
Application: Useful in depicting SNPs at the genomic level.

c. p. Nomenclature (Protein Level)
Basis: Nomenclature and Symbolism for Amino Acids and Peptides (IUPAC-IUB)
Format: "p.[position]S>N" (e.g., "NM_004006.2:p.4375S>N")
Relevance: Essential in describing protein-level sequence variants.

d. Indels (Insertions and Deletions)
DNA Format: "g.123_127delinsAG"
Note: The term "indel" is avoided in HGVS nomenclature due to its ambiguous meaning across different disciplines.

Significance in Clinical Diagnostics and Research

The HGVS nomenclature is invaluable in clinical settings and research. It ensures that genetic variants are described in a way that is universally understood, facilitating communication and collaboration among scientists and healthcare professionals. This clarity is crucial for advancing our understanding of genetics in health and disease.

Conclusion

The HGVS nomenclature is more than a mere set of rules; it's a language that unites the global scientific community in its quest to decipher the complexities of the human genome. By adopting this standardized approach, researchers and clinicians can share and interpret genetic data with precision, paving the way for breakthroughs in genetic research and personalized medicine.