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Analysis of p.Ile1234Val variant, CFTR gene, CF Transmembrane conductance Regulator protein (1480 residues)


Data provided and calculated by CYSMA must be considered as predictions.
They are meant for educational purposes only and are provided with NO WARRANTY with respect to their biological reliability.



  • Allele frequency:

    variant I1234V gnomAD (123,136 exomes): 4.02e-06


  • Ortholog conservation: Help


    Number of sequences AAPI* AAPIR** Number of divergencies Number of mutant V1234 Number of gaps Conservation of I1234 Conservation - gap
    50 80.72% 83.87% 8
    show divergencies
    5
    details
    0
    details
    84.00% (42 / 50) 84.00% (42 / 50)



    The wild-type residue I1234 is highly conserved among the CFTR orthologs: 84% (42 / 50 CFTR orthologs)
    The variant I1234V has been found among the CFTR orthologs with a high frequency: 10% (5 / 50 CFTR orthologs)

    *AAPI: Alignment Average Percentage Identity
    **AAPIR: Alignment Average Percentage Identity of the Region (20 residues surrounding position 1234). AAPIR appears in green if it is more than 10% compared to AAPI, in red if less than 10%.
    Click here for more details on the alignment.


    CYSMA's visualizing modules for Ortholog conservation:





    ⬇ Download the region alignment (50 residues, Fasta format)
    ⬇ Download the CFTR phylogenic tree



    Display methods


  • Domain conservation: Help

    The domain NBD2 of CF Transmembrane conductance Regulator has been shown to interact with:


    The residue p.Ile1234 belongs to the domain NBD2.

    1210
    1443


    NBD2: is the nucleotide binding domain 2, also called the ATP-binding cassette (ABC).
    It contains the Walker A (P-loop) and Walker B motifs, the C-motif (also known as the signature sequence), the A-, D-, Q-, and H-loops.








    NBD2 of CF Transmembrane conductance Regulator domain alignment including p.Ile1234 residue.



    Number of sequences AAPID***
    (from aa 1210 to aa 1443)
    AAPIR! Number of divergencies Number of mutant Number of gaps Conservation of I1234 Conservation - gap
    715 24.58% 28.82% 495
    show divergencies
    225 0 30.77% (220 / 715) 30.77% (220 / 715)



    ***AAPID: Alignment Average Percentage Identity of the Domain (positions are indicated).
    !AAPIR: Alignment Average Percentage Identity of the Region (20 residues surrounding position 1234). AAPIR appears in green if it is more than 10% compared to AAPID, in red if less than 10%.

    The wild-type residue I1234 belongs to the NBD2 domain and is conserved at 30.77% among the NBD2 homologs (220 / 715 NBD2 homologs)
    The variant I1234V has been found among the NBD2 homologs with a very high frequency: 31.47% (225 / 715 NBD2 homologs)

    Divergencies show the amino acids which have been selected in the evolution. Residues present in more than 10% of the sequences are highlighted in blue.
    Please note that CYSMA does not consider splicing alterations.
    Refer to the Help page for more details.



    CYSMA's visualizing modules for NBD2 domain conservation:





    Display methods


  • Refer to the Help page for more details.


  • Secondary structure analysis: Help


    Residue p.Ile1234 is predicted to belong to a β strand. Probability is 0.932.

    Direct environment is as follow:

    ISFSI1234SPGQ
    CEEEEECCC


    Observed frequencies in β strands:
    I: 1.6
    V: 1.8

    Mutant residue is more observed in this type of structure.

    Display methods











  • 3D analysis: Help


    Models provided and analysed by CYSMA must be considered as predictions, therefore be careful when interpreting the results. All efforts have been made to build structures of quality, however, they are provided with NO WARRANTY as to their accuracy with the real biological molecules studied.

    Wild type and predicted mutant structures have been compared. You will find the results below.


  • Clinical significance:

    The variant I1234V has been been described as Pathogenic - reviewed by expert panel - (ClinVar for more details)


  • Patients data: CFTR-France

  • Variant I1234V might correspond to:


    Variant details from CFTR-France:
    Name NM_000492.3:c.3700A>G
    Protein name NP_000483.3:p.(Ile1234Val)
    Genomic name chr7:g.117267807A>G
    Class disease-causing


    Patients carrying this variant in CFTR-France:
    Total number of patients 7
    CF 6
    CFTR-RD1
    • CBAVD  1

    (CFTR-France for more details)




  • Additional resources:



  • References


    CYSMA has completed its calculations; Execution time: 12 wallclock secs ( 8.13 usr 0.03 sys + 3.34 cusr 0.06 csys = 11.56 CPU)