UniProtKB/Swiss-Prot P51787: Variant p.Arg533Trp

Potassium voltage-gated channel subfamily KQT member 1
Gene: KCNQ1
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Variant information Variant position:

533 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

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:

From Arginine (R) to Tryptophan (W) at position 533 (R533W, p.Arg533Trp). 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 basic (R) to large size and aromatic (W) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-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:

In LQT1; minor changes of wt current (homomultimers); positive voltage shift of the channel activation (heteromultimers). Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs199472793 [ dbSNP | Ensembl ]

Sequence information Variant position:

533 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

676 The length of the canonical sequence.
Location on the sequence:

TIKVIRRMQYFVAKKKFQQA R KPYDVRDVIEQYSQGHLNLM 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                         TIKVIRRMQYFVAKKKFQQARKPYDVRDVIEQYSQGHLNLM

Mouse                         TIKVIRRMQYFVAKKKFQQARKPYDVRDVIEQYSQGHLNLM

Rat                           TIKVIRRMQYFVAKKKFQQARKPYDVRDVIEQYSQGHLNLM

Pig                           TIKVIRRMQYFVAKKKFQQARKPYDVRDVIEQYSQGHLNLM

Rabbit                        TVKVIRRMQYFVAKKKFQQARKPYDVRDVIEQYSQGHLNLM

Xenopus laevis                AIKVIRRMQYFVAKKKFQQARKPYDVRDVIEQYSQGHLNLM

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 – 676	Potassium voltage-gated channel subfamily KQT member 1
Topological domain	349 – 676	Cytoplasmic
Mutagenesis	516 – 516	V -> D. Reduced protein expression, probably due to misfolding and proteasomal degradation. Significantly reduced electrophysiological activity. Reduced electrophysiological activity in the presence of KCNE1.
Mutagenesis	526 – 526	K -> N. Decreased interaction with PIP2 and calmodulin/CALM in the presence of calcium. Insensitive to gating modulation by calcified CALM. Impaired IKS current. Decreased interaction with PIP2 and CALM in the presence of calcium; when associated with N-527. Increased binding to PIP2 and CALM in the absence of calcium. Increased binding to CALM and no change in PIP2 binding in the absence of calcium; when associated with N-527.
Mutagenesis	527 – 527	K -> N. Decreased interaction with PIP2 and calmodulin/CALM in the presence of calcium. Decreased interaction with PIP2 and CALM in the presence of calcium; when associated with N-526. Increased binding to PIP2 and CALM in the absence of calcium. Increased binding to CALM and no change in PIP2 binding in the absence of calcium; when associated with N-526.

Literature citations
Novel mutations in KvLQT1 that affect Iks activation through interactions with Isk.
Chouabe C.; Neyroud N.; Richard P.; Denjoy I.; Hainque B.; Romey G.; Drici M.-D.; Guicheney P.; Barhanin J.;
Cardiovasc. Res. 45:971-980(2000)
Cited for: VARIANTS LQT1 GLN-190; TRP-533 AND TRP-539; VARIANT JLNS1 HIS-243; CHARACTERIZATION OF VARIANTS LQT1 GLN-190; TRP-533 AND TRP-539; CHARACTERIZATION OF VARIANT JLNS1 HIS-243; Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test.
Kapplinger J.D.; Tester D.J.; Salisbury B.A.; Carr J.L.; Harris-Kerr C.; Pollevick G.D.; Wilde A.A.; Ackerman M.J.;
Heart Rhythm 6:1297-1303(2009)
Cited for: VARIANTS LQT1 VAL-2; SER-7; THR-46; 64-PRO--PRO-70 DEL; PHE-66; THR-73; CYS-111; LEU-117; LEU-127; ILE-133; PRO-134; ALA-144; MET-153; MET-162; ARG-168; MET-172; CYS-174; HIS-174; THR-178; SER-179; HIS-184; ARG-186; GLN-190; LEU-190; TRP-195; VAL-198; ALA-199; MET-204; MET-215; MET-224; LEU-225; CYS-231; HIS-231; ASN-235; GLY-241; ASN-242; CYS-243; PRO-250; MET-254; CYS-259; LEU-259; VAL-262; PRO-266; SER-268; ASP-269; SER-269; ASP-272; PHE-273; VAL-274; LEU-277; PRO-277; GLU-280; CYS-281; PRO-282; GLY-283; ASP-292; CYS-293; GLU-302; VAL-302; PRO-303; ARG-305; SER-305; ARG-306; ILE-312; CYS-314; SER-314; CYS-315; VAL-316; SER-320; ALA-322; MET-322; ARG-325; TYR-339; GLU-341; GLY-341; VAL-341; PHE-342; LEU-343; ARG-350; SER-351; ARG-354; MET-360; ARG-362; HIS-365; GLN-366; TRP-366; HIS-374; GLY-379; LYS-385; PRO-389; THR-391 INS; TRP-397; ARG-398; GLU-446; LEU-448; TRP-451; SER-460; LEU-477; TRP-511; GLN-518; ARG-520; SER-522; GLY-524; THR-525; VAL-525; TRP-533; GLN-539; TRP-539; ILE-541; LYS-543; LEU-546; ARG-547; CYS-555; HIS-555; SER-555; GLU-557; PHE-566; PRO-566; TYR-566; THR-567; ARG-568; GLU-569; LEU-571; MET-587; ASP-589; CYS-591; HIS-591; GLN-594; PRO-594; GLU-596 DEL; LYS-596; MET-600; ASN-611; HIS-614 DEL; SER-626 AND ARG-635;

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.