UniProtKB/SwissProt variant VAR

Variant information

Variant position:

36

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

Type of variant:

Unclassified

The variants are classified into three categories: Disease, Polymorphism and Unclassified.

Disease: Variants implicated in disease according to literature reports.
Polymorphism: Variants not reported to be implicated in disease.
Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:

From Arginine (R) to Histidine (H) at position 36 (R36H, p.Arg36His).

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 (H)

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

Involvement in disease:

Long QT syndrome 5 (LQT5) [MIM:613695]: A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. {ECO:0000269|PubMed:10400998, ECO:0000269|PubMed:10973849, ECO:0000269|PubMed:11692163, ECO:0000269|PubMed:16414944, ECO:0000269|PubMed:19716085, ECO:0000269|PubMed:25037568, ECO:0000269|PubMed:9354802, ECO:0000269|PubMed:9445165}. Note=The disease is caused by mutations affecting the gene represented in this entry.

The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

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 rs199473351 [ dbSNP | Ensembl ]

Sequence information

Variant position:

36

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:

LWQETVQQGGNMSGLARRSP R SSDGKLEALYVLMVLGFFGF

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                         LWQETVQQGGNMSG-LARRSPRSSDGKLEALYVLMVLGFFGF

Mouse                         LWQETAEQGGNVSG-LARKSQLRDDSKLEALYILMVLGFFG

Rat                           LWQETDEPGGNMSADLARRSQLRDDSKLEALYILMVLGFFG

Pig                           LWQETDEPGGNMSADLARRSQLRDDSKLEALYILMVLGFFG

Rabbit                        LGEETAHLQGSSATSLARRGPLGDDGQMEALYILMVLGFFG

Cat                           LWQGTAHQGGNTSG-LARRSPGGDDSQLEALYILMVLGFFG

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
Site	19 – 19	Interacts with the scolopendra toxin SSD609
Glycosylation	26 – 26	N-linked (GlcNAc...) asparagine
Mutagenesis	19 – 19	E -> K. Loss inhibition of the complex KCNQ1-KCNE1 by the scolopendra toxin SSD609.
Mutagenesis	28 – 28	S -> T. No measurable effect on assembly with KCNQ1 or cell surface expression of the KCNE1/KCNQ1 channel complex, and loss of glycosylation at N-5; when associated with Q-5. 50% reduction of cell surface expression of the KCNE1/KCNQ1 channel complex, and loss of glycosylation at N-5 and T-7; when associated with A-7.
Mutagenesis	32 – 32	R -> D. Increase in inhibition of the complex KCNQ1-KCNE1 by the scolopendra toxin SSD609.

Literature citations

Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice.
Napolitano C.; Priori S.G.; Schwartz P.J.; Bloise R.; Ronchetti E.; Nastoli J.; Bottelli G.; Cerrone M.; Leonardi S.;
JAMA 294:2975-2980(2005)
Cited for: VARIANTS LQT5 HIS-36 AND SER-53;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P15382: Variant p.Arg36His