UniProtKB/Swiss-Prot P13569: Variant p.Phe693Leu

Cystic fibrosis transmembrane conductance regulator
Gene: CFTR
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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; uncertain significance; no effect on glycan maturation; no effect on channel activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs145540754 [ dbSNP | Ensembl ]
Variant rs397508338 [ dbSNP | Ensembl ]

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                         -DSSAPWSKP-KQSFRQTGE-----VGEKRKNSILNSFSSV

Rat                           -DASTTWNKA-KQSFRQTGE-----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.

Type	Positions	Description
Chain	1 – 1480	Cystic fibrosis transmembrane conductance regulator
Topological domain	359 – 858	Cytoplasmic
Region	654 – 831	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; Characterization of 19 disease-associated missense mutations in the regulatory domain of the cystic fibrosis transmembrane conductance regulator.
Vankeerberghen A.; Wei L.; Jaspers M.; Cassiman J.-J.; Nilius B.; Cuppens H.;
Hum. Mol. Genet. 7:1761-1769(1998)
Cited for: CHARACTERIZATION OF VARIANTS CF PHE-601; SER-610; THR-613; GLY-614; THR-618; SER-619; GLN-620; PRO-620; ARG-628; PRO-633; SER-665; LEU-693 AND LYS-822; CHARACTERIZATION OF VARIANTS CBAVD ASP-622; MET-766; GLY-792; GLY-800 AND MET-807; CHARACTERIZATION OF VARIANT THORACIC SARCOIDOSIS LYS-826; 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.