Polymorphisms, mutations and their molecular consequences
Polymorphism versus mutation versus variant, germline and somatic change, variant types and their effect on protein, loss and gain of function, and how to read HGVS notation.
Tier 2Medical sciences concept
Written with AI assistance and fact-checked against the sources below. For exam study, not clinical decisions. How notes are made
At a glance
- Every person carries about 4 to 5 million differences from the reference genome. Almost all are harmless.
- Polymorphism: a variant with allele frequency ≥1% in a population. Mutation traditionally meant a rarer change, or the event that created a new change.
- Both words mix frequency with harm. Since the 2015 ACMG/AMP standards, reports use variant plus a five-tier class: pathogenic, likely pathogenic, uncertain significance (VUS), likely benign, benign.
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Sources
- Thompson & Thompson Genetics and Genomics in Medicine (9th ed.)Elsevier (Cohn, Scherer and Hamosh, eds), 2023
- HGVS Nomenclature 2024: improvements to community engagement, usability, and computabilityGenome Medicine (Hart et al., 2024;16:149), 2024
- Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the ACMG and AMPGenetics in Medicine (Richards et al., 2015;17:405-24), 2015
- Iron-overload-related disease in HFE hereditary hemochromatosisNew England Journal of Medicine (Allen et al., 2008;358:221-30), 2008
- Last updated
- 14 November 2026
What changed
- 14 November 2026 Personal emails, About story and Australian-style copy