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User Question 4 : Functional analysis of a SNP

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Sample User Question back to top

A gene variant primarily found in African Americans, that slightly increases the risk for developing an irregular heartbeat, known as arrhythmia. The variant occurs in the cardiac sodium channel gene SCN5A that results a change of amino acid at the position of 1102 from serine to tyrosine (S To Y). Can you predict the effect of this non-synonymous SNP (rs7626962)?

Flow Chart back to top

  1. Entrez SNP - Search Entrez SNP by refSNP ID to find SNP information.
    Down Arrow
  2. Entrez Protein - Find protein information including its amino acid sequence and the presence of functional domains

    3. Down Arrow
  3. NCBI Amino Acid Explorer - Compare amino acids in terms of physyo-chemical properties

    4. Down Arrow
  4. NCBI Mutation Analyzer - Predict the effect of amino acid change on the protein structure

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  5. TMHMM Server v. 2.0 - Predict the presence of transmembrane helix in a protein sequence

    6. Down Arrow
  6. Russel etal., Amino Acid Properties Table - Predict the effect of amino acid change on the protein structure

Step By Step Guide back to top

  1. Entrez SNP
    • Enter "rs7626962" in the search box and click on "GO"
    • Click on "GeneView" and note the amino acid change at 1102 position
    • Click on "NP_000326" appears in Protein column in GeneView to view the protein information of SCN5A present in Entrez Protein database

  2. Entrez Protein
    • Select "FASTA" from "Display" drop-down menu and click on "Display" to get amino acid sequence for SCN5A
    • Click on "Domains" to see the presence of conserved domains in the protein sequence
    • Select the domain, which covers the amino acid position 1102 and click on the domain to view the sequence alignment. Check whether "Ser" at position 1102 is conserved among the family members or not

  3. NCBI Amino Acid Explorer
    • Go to "Compare" option appears in the left side bar and select "S-Ser" to "Y-Tyr" and click "Compare"
  4. NCBI Mutation Analyzer
    • Select "ser" to "tyr" and click on "Mutate" button"
    • In the "results of mutating serine to tyrosine" page note the color which indicates the amino acid substitution score based on BLOSUM62 matrix
  5. TMHMM Server v. 2.0
    • Copy the FASTA formatted sequence for SCN5A from Entrez Protein step and paste it into the sequence submission box
    • Select output format "Extensive, with graphics" and click "Submit"
    • Find the topology (transmembrane helix/inside/outside) around position 1102
  6. Russel etal., Amino Acid Properties Table
    • Click on "S" present in the "Overview of Amino Acid Properties" figure
    • Check the substitution score for ser to tyr


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