Mutation assessor


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Reference: Reva B., Antipin Y., Sander C. Predicting the functional impact of protein mutations: Applications to cancer genomics. Nucleic Acids Res. (2011)
Hosted: Hosted by the Computational Biology Center, Memorial Sloan Kettering Cancer Center. (http://mutationassessor.org/v1)

Summary:
Mutation assessor uses a multiple sequence alignment (MSA), partitioned to reflect functional specificity, and generates conservation scores for each column to represent the functional impact of a missense variant.

Methodology:
• Mutation assessor accepts a UniProt protein accession, a RefSeq protein ID or transcript ID along with the query variant.
• A partitioned MSA is created with the aim of identifying evolutionary conserved positions that contribute to protein functional specificity.
• A conservation score is combined with a specificity score to determine a functional impact score. Variants classed as ‘neutral’ or ‘low’ are predicted to not impact protein function, whereas variants classed as ‘medium’ or ‘high’ are predicted to result in altered function.

Input:
Mutation assessor creates its own MSA using UniProt protein sequences. This is then partitioned based on UniProt and Pfam domain boundaries and 3D structures are used to produce aligned sets of families and subfamilies. The user cannot upload an alignment.