UniProtKB/SwissProt variant VAR

Variant information

Variant position:

1595

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

Type of variant:

Disease [Disclaimer]

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 Aspartate (D) to Asparagine (N) at position 1595 (D1595N, p.Asp1595Asn).

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 medium size and acidic (D) to medium size and polar (N)

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

Involvement in disease:

Progressive familial heart block 1A (PFHB1A) [MIM:113900]: A cardiac bundle branch disorder characterized by progressive alteration of cardiac conduction through the His-Purkinje system, with a pattern of a right bundle-branch block and/or left anterior hemiblock occurring individually or together. It leads to complete atrio-ventricular block causing syncope and sudden death. {ECO:0000269|PubMed:11234013, ECO:0000269|PubMed:11804990, ECO:0000269|PubMed:12569159, ECO:0000269|PubMed:12574143, ECO:0000269|PubMed:19251209, ECO:0000269|PubMed:23420830}. 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 PFHB1A; significant defect in the kinetics of fast-channel inactivation distinct from mutations reported in LQT3.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs137854607 [ dbSNP | Ensembl ]

Sequence information

Variant position:

1595

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

Protein sequence length:

2016

The length of the canonical sequence.

Location on the sequence:

CIVKLAALRHYYFTNSWNIF D FVVVILSIVGTVLSDIIQKY

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                         CIVKLAALRHYYFTNSWNIFDFVVVILSIVGTVLSDIIQKY

Mouse                         CIVKMAALRHYYFTNSWNIFDFVVVILSIVGTVLSDIIQKY

Rat                           CIVKMAALRHYYFTNSWNIFDFVVVILSIVGTVLSDIIQKY

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 – 2016	Sodium channel protein type 5 subunit alpha
Transmembrane	1590 – 1607	Helical; Name=S3 of repeat IV
Repeat	1510 – 1807	IV
Alternative sequence	1573 – 1604	Missing. In isoform 3.
Mutagenesis	1610 – 1610	D -> A. Complete loss of channel inhibition by the spider toxin Jingzhaotoxin-I.
Mutagenesis	1610 – 1610	D -> R. High decrease in affinity to the sea anemone toxin anthopleurin-B.
Mutagenesis	1614 – 1614	K -> A. 4.2-fold decrease of channel inhibition potency by the spider toxin Jingzhaotoxin-I.

Literature citations

Clinical, genetic and biophysical characterisation of SCN5A mutations associated with atrioventricular conduction block.
Wang D.W.; Viswanathan P.C.; Balser J.R.; George A.L. Jr.; Benson D.W.;
Circulation 105:341-346(2002)
Cited for: CHARACTERIZATION OF VARIANTS PFHB1A SER-298 AND ASN-1595;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q14524: Variant p.Asp1595Asn