Genetics / gene-constraint scoring · BEGINNER LESSON
RVIS
RVIS, the Residual Variation Intolerance Score, is a gene-level score for protein-coding human genes that ranks how much common functional genetic variation a gene seems to tolerate. Lower RVIS values mean the gene has less common functional variation than expected and is more mutation-intolerant.
What RVIS is
RVIS stands for Residual Variation Intolerance Score. It is a gene-level assessment for protein-coding human genes. The score ranks genes by how much common functional genetic variation they contain compared with what would be statistically expected, given the amount of variation that appears to be neutral in that gene. In simple terms, RVIS asks whether a gene has fewer or more common functional variants than expected.
[1] Beyond the Very Important Pharmacogenes (VIPs) - PMC [2] The intolerance to functional genetic variation of protein domains ... [3] Ionotropic GABA and Glutamate Receptor Mutations and Human ...
How to read the score
A negative RVIS value means the gene has less common functional variation than predicted, which is interpreted as stronger selection against changes that alter function and therefore lower tolerance to mutation. A positive RVIS value means the gene has more common functional variation than predicted, which is interpreted as higher tolerance to functional variation. Lower RVIS values mark more intolerant genes. This same idea has also been extended to sub-regions of genes, such as protein domains and exons, where lower subRVIS scores indicate more intolerant regions.
[1] Beyond the Very Important Pharmacogenes (VIPs) - PMC [2] The intolerance to functional genetic variation of protein domains ...
What RVIS can and cannot do
RVIS is used to help rank genes for their likely sensitivity to functional change, and lower scores have been linked with pathogenic mutations in some studies. The sources also note limits: analyses may involve only selected gene sets, and results can depend on the network or regional method used. RVIS does not by itself prove that a specific variant is disease-causing; it is one piece of evidence about whether a gene or region tends to resist functional variation.
[1] Beyond the Very Important Pharmacogenes (VIPs) - PMC [2] The intolerance to functional genetic variation of protein domains ... [3] Ionotropic GABA and Glutamate Receptor Mutations and Human ...
SEE THE IDEA
How RVIS summarizes gene intolerance
The number of common variants actually found in a gene.
The amount of variation expected after accounting for presumably neutral variation.
A comparison of observed versus expected variation; lower values mean more intolerance.
Observed variation is compared with expected variation to produce a score that ranks genes by intolerance.
RVIS turns a comparison of observed and expected functional variation into a gene-level intolerance ranking.
TRY IT YOURSELF
Test your understanding
Choose an answer, then check the explanation.
PUT IT TOGETHER
Match each concept to its meaning
Drag a label onto its description, or select a label and then select a description. This also works with a keyboard.
4 pairs to match
Sources and further reading
This general lesson was generated from public source material. It explains a concept; it does not interpret a private paper or provide medical advice.