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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P51787: Variant p.Trp248Arg

Potassium voltage-gated channel subfamily KQT member 1
Gene: KCNQ1
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Variant information Variant position: help 248 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] 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: help From Tryptophan (W) to Arginine (R) at position 248 (W248R, p.Trp248Arg). 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: help Change from large size and aromatic (W) to large size and basic (R) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -3 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: help In LQT1; slower rate of activation and voltage dependence of activation-inactivation shifted to more positive potentials (homomultimers); channels non-functional (heteromultimers). Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 248 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 676 The length of the canonical sequence.
Location on the sequence: help RGIRFLQILRMLHVDRQGGT W RLLGSVVFIHRQELITTLYI 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         RGIRFLQILRMLHVDRQGGTWRLLGSVVFIHRQELITTLYI

Mouse                         RGIRFLQILRMLHVDRQGGTWRLLGSVVFIHRQELITTLYI

Rat                           RGIRFLQILRMLHVDRQGGTWRLLGSVVFIHRQELITTLYI

Pig                           RGIRFLQILRMLHVDRQGGTWRLLGSVVFIHRQELITTLYI

Rabbit                        RGIRFLQILRMLHVDRQGGTWRLLGSVVFIHRQELITTLYI

Xenopus laevis                RGIRFLQILRMLHVDRQGGTWRLLGSVVFIHRQELITTLYI
Sequence annotation in neighborhood: help 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 – 676 Potassium voltage-gated channel subfamily KQT member 1
Transmembrane 226 – 248 Helical; Voltage-sensor; Name=Segment S4
Mutagenesis 231 – 231 R -> A. Strongly inhibits SLC5A3 transporter activity.
Helix 246 – 284



Literature citations
Long QT syndrome-associated mutations in the S4-S5 linker of KvLQT1 potassium channels modify gating and interaction with minK subunits.
Franqueza L.; Lin M.; Shen J.; Keating M.T.; Sanguinetti M.C.;
J. Biol. Chem. 274:21063-21070(1999)
Cited for: CHARACTERIZATION OF VARIANTS LQT1 CYS-243; ARG-248 AND LYS-261; Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2.
Splawski I.; Shen J.; Timothy K.W.; Lehmann M.H.; Priori S.G.; Robinson J.L.; Moss A.J.; Schwartz P.J.; Towbin J.A.; Vincent G.M.; Keating M.T.;
Circulation 102:1178-1185(2000)
Cited for: VARIANTS LQT1 CYS-111; LYS-160; ARG-168; HIS-174; SER-179; SER-184; PRO-194; LEU-225; CYS-243; ARG-248; MET-254; PRO-266; ASP-269; PHE-273; ILE-310; ILE-312; ARG-325; GLU-341; VAL-341; TRP-349; GLN-366; ILE-391; ARG-448; PHE-566; CYS-583 AND GLN-594;
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.