UniProtKB/SwissProt variant VAR

Variant information

Variant position:

67

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 Arginine (R) to Cysteine (C) at position 67 (R67C, p.Arg67Cys).

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 (C)

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 LQT5; unknown pathological significance.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs199473645 [ dbSNP | Ensembl ]

Sequence information

Variant position:

67

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

Protein sequence length:

129

The length of the canonical sequence.

Location on the sequence:

VLMVLGFFGFFTLGIMLSYI R SKKLEHSNDPFNVYIESDAW

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                         VLMVLGFFGFFTLGIMLSYIRSKKLEHSNDPFNVYIESDAW

Mouse                         ILMVLGFFGFFTLGIMLSYIRSKKLEHSHDPFNVYIESDAW

Rat                           ILMVLGFFGFFTLGIMLSYIRSKKLEHSHDPFNVYIESDAW

Pig                           ILMVLGFFGFFTLGIMLSYIRSKKLEHSHDPFNVYIESDAW

Rabbit                        ILMVLGFFGFFTLGIMLSYIRSQKLEHSHDPFNVYIEANDW

Cat                           ILMVLGFFGFFTLGIMLSYIRSKKLEHSHDPFNVYIESDTW

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 – 129	Potassium voltage-gated channel subfamily E member 1
Topological domain	67 – 129	Cytoplasmic
Mutagenesis	69 – 69	K -> H. Lowers current 2-fold and leads to faster deactivation of KCNQ1/KCNE1 channel.
Helix	46 – 71

Literature citations

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 LQT5 VAL-8; MET-10; LEU-28; HIS-32; SER-55; PRO-58; PRO-59; CYS-67; HIS-67; MET-70; ASN-76; LYS-83 AND MET-125;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P15382: Variant p.Arg67Cys