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UniProtKB/Swiss-Prot P13569: Variant p.Phe693Leu

Cystic fibrosis transmembrane conductance regulator
Gene: CFTR
Variant information

Variant position:  693
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  US
The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change:  From Phenylalanine (F) to Leucine (L) at position 693 (F693L, p.Phe693Leu).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from large size and aromatic (F) to medium size and hydrophobic (L)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Variant description:  In CF; unknown pathological significance.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  693
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1480
The length of the canonical sequence.

Location on the sequence:   GDAPVSWTETKKQSFKQTGE  F GEKRKNSILNPINSIRKFSI
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         GDAPVSWTETKKQSFKQTGE-----FGEKRKNSILNPINSIRKFSI

Gorilla                       GDAPVSWTETKKQSFKQTGE-----FGEKRKNSILNPINSI

                              GDAAVPWNETKKQSFKQTGE-----FGEKRKNSILNPINSI

Rhesus macaque                GDAPVSWTETKKQSFKQTGE-----FGEKRKNSILNPINSI

Chimpanzee                    GDAPVSWTETKKQSFKQTGE-----FGEKRKNSILNPINSI

Mouse                         -DSSAPWSKPKQS-FRQTGE-----VGEKRKNSILNSFSSV

Rat                           -DASTTWNKAKQS-FRQTGE-----FGEKRKNSILSSFSSV

Pig                           GDASVSWNETKKQSFKQTGE-----FGEKRKNSILNSINSI

Bovine                        GDTSVSWNETKKPSFKQTGE-----FGEKRKNSILSSINSI

Rabbit                        GDASISWNDTRKQSFKQNGE-----LGEKRKNSILNPVNSM

Sheep                         GDTSVSWNETKKPSFKQTGE-----FGEKRKNSILNSINSI

Horse                         GDATVSWNETKKQSFKQTGE-----FGDKRKNSILNPINSI

Xenopus laevis                SDPSAVRNEVKNKSFKQVAD-----FTEKRKSSIINPRKSS

Zebrafish                     ESAGM---QPERSAFRQVPPTKPMYIDERKASVIVNPLGVA

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 1 – 1480 Cystic fibrosis transmembrane conductance regulator
Topological domain 359 – 858 Cytoplasmic
Region 654 – 831 Intrinsically disordered R region
Modified residue 686 – 686 Phosphoserine; by PKC
Modified residue 700 – 700 Phosphoserine; by PKA
Modified residue 712 – 712 Phosphoserine; by PKA
Cross 688 – 688 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Alternative sequence 606 – 1480 Missing. In isoform 3.


Literature citations

Identification of three novel cystic fibrosis mutations in a sample of Italian cystic fibrosis patients.
Audrezet M.P.; Novelli G.; Mercier B.; Sangiuolo F.; Maceratesi P.; Ferec C.; Dallapiccola B.;
Hum. Hered. 43:295-300(1993)
Cited for: VARIANT CF LEU-693;

Variant cystic fibrosis phenotypes in the absence of CFTR mutations.
Groman J.D.; Meyer M.E.; Wilmott R.W.; Zeitlin P.L.; Cutting G.R.;
N. Engl. J. Med. 347:401-407(2002)
Cited for: VARIANT CF LEU-693;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.