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Analysis of p.Ile807Met 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 I807M gnomAD (123,136 exomes): 7.59e-04; variant I807M gnomAD (15,496 genomes): 2.58e-04


  • Ortholog conservation: Help


    Number of sequences AAPI* AAPIR** Number of divergencies Number of mutant M807 Number of gaps Conservation of I807 Conservation - gap
    50 80.72% 71.97% 1
    show divergencies
    0
    details
    1
    details
    96.00% (48 / 50) 97.96% (48 / 49)


    The wild-type residue I807 is highly conserved among the CFTR orthologs: 96% (48 / 50 CFTR orthologs)
    The variant I807M has never been found among the CFTR orthologs

    *AAPI: Alignment Average Percentage Identity
    **AAPIR: Alignment Average Percentage Identity of the Region (20 residues surrounding position 807). 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 residue p.Ile807 belongs to the domain R.

    650
    842


    R: the regulatory (R) domain links the two transporter halves (MSD1-NBD1 and MSD2-NBD2). It is a highly flexible region and it contains multiple phosphorylation sites, which are the target of Protein Kinase A and B (PKA and PKC), and control the gating and traffiking of the chloride chanel.








    R of CF Transmembrane conductance Regulator domain alignment including p.Ile807 residue.



    Number of sequences AAPID***
    (from aa 650 to aa 842)
    AAPIR! Number of divergencies Number of mutant Number of gaps Conservation of I807 Conservation - gap
    47 73.27% 73.54% 1
    show divergencies
    0 0 97.87% (46 / 47) 97.87% (46 / 47)



    ***AAPID: Alignment Average Percentage Identity of the Domain (positions are indicated).
    !AAPIR: Alignment Average Percentage Identity of the Region (20 residues surrounding position 807). AAPIR appears in green if it is more than 10% compared to AAPID, in red if less than 10%.

    The wild-type residue I807 belongs to the R domain and is conserved at 97.87% among the R homologs (46 / 47 R homologs)
    The variant I807M has never been found among the R 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 R domain conservation:





    Display methods


  • Refer to the Help page for more details.


  • Secondary structure analysis: Help


    Residue p.Ile807 is predicted to belong to a loop. Probability is 0.603.

    Direct environment is as follow:

    TELDI807YSRR
    CCCCCCCCC


    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 I807M has been been described as Conflicting interpretations of pathogenicity - criteria provided, conflicting interpretations - (ClinVar for more details)


  • Patients data: CFTR-France

  • Variant I807M might correspond to:


    Variant details from CFTR-France:
    Name NM_000492.3:c.2421A>G
    Protein name NP_000483.3:p.(Ile807Met)
    Genomic name chr7:g.117232642A>G
    Class disease-causing


    Patients carrying this variant in CFTR-France:
    Total number of patients 9
    Asymptomatic compound heterozygote 2
    CFTR-RD7
    • CBAVD  3
    • Other  1
    • Pancreatitis  3

    (CFTR-France for more details)




  • Additional resources:



  • References


    CYSMA has completed its calculations; Execution time: 11 wallclock secs ( 7.70 usr 0.03 sys + 3.02 cusr 0.06 csys = 10.81 CPU)