UniProtKB/Swiss-Prot P51787 : Variant p.Arg594Gln
Potassium voltage-gated channel subfamily KQT member 1
Gene: KCNQ1
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Variant information
Variant position:
594
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:
LP/P [Disclaimer : Variants classification is intended for research purposes only, not for clinical and diagnostic use . The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant. ]
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 Glutamine (Q) at position 594 (R594Q, p.Arg594Gln).
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 medium size and polar (Q)
The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:
1
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.
Any additional useful information about the variant.
Other resources:
Links to websites of interest for the variant.
Sequence information
Variant position:
594
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:
ISVSEKSKDRGSNTIGARLN
R VEDKVTQLDQRLALITDMLH
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 ISVSEKSKDRGSNTIGARLNR VEDKVTQLDQRLALITDMLH
Mouse IPISEKSKDRGSNTIGARLNR VEDKVTQLDQRLVIITDMLH
Rat IPISEKSKDRGSNTIGARLNR VEDKVTQLDQRLVIITDMLH
Pig ISSSEKVKDRGSNTIGARLNR VEDKVTQLDQRLELITDMLQ
Rabbit VPISEKSKDRGSNSIGARLNR VEDKVTQLDQRLVLIADMLQ
Xenopus laevis LSVSDKVKDKGINTIGSRLNR VEDKVTQMDHKLNLITDMLH
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
Region
588 – 616
Interaction with AKAP9
Region
589 – 620
C-terminal assembly domain
Coiled coil
585 – 621
Mutagenesis
589 – 589
G -> M. No effect.
Mutagenesis
590 – 590
A -> W. Reduced cell surface expression and strongly reduced potassium current.
Mutagenesis
593 – 593
N -> G. Reduced cell surface expression and moderately reduced potassium current.
Mutagenesis
602 – 602
L -> A. Does not interact with AKAP9 and the targeting protein kinase A (PKA) catalytic subunit and protein phosphatase 1 (PP1); when associated with I-609.
Mutagenesis
609 – 609
I -> A. Does not interact with AKAP9 and the kinase A (PKA) catalytic subunit and protein phosphatase 1 (PP1); when associated with L-602.
Helix
588 – 609
Literature citations
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;
Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing.
Tester D.J.; Will M.L.; Haglund C.M.; Ackerman M.J.;
Heart Rhythm 2:507-517(2005)
Cited for: VARIANTS LQT1 71-ALA--PRO-73 DEL; THR-73; GLY-115; TYR-122; ILE-133; PHE-136; LYS-160; ARG-168; CYS-174; GLN-190; PHE-204; LEU-225; ASN-235; ASN-242; CYS-243; MET-254; 254-VAL--PHE-256 DEL; CYS-259; LEU-259; ASP-261; PRO-266; SER-269; ASP-269; PHE-273; ARG-273; SER-276 DEL; LEU-277; HIS-278; LYS-290; ASP-292; CYS-293; VAL-302; ARG-304; SER-305; ILE-312; SER-314; ARG-314; ASP-314; CYS-315; ARG-316; ALA-322; PHE-339 DEL; VAL-341; SER-343; GLU-344; VAL-344; GLU-345; TRP-349; PRO-353; ARG-362; TRP-366; HIS-374; SER-380; TYR-389; TRP-452; GLY-524; GLU-526; TRP-539; LEU-546; CYS-555; HIS-555; TYR-566; SER-567; ARG-568; MET-587; THR-590; HIS-591; GLN-594; MET-619 AND SER-626;
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.