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UniProtKB/Swiss-Prot Q14524: Variant p.Gly298Ser

Sodium channel protein type 5 subunit alpha
Gene: SCN5A
Variant information

Variant position:  298
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 Glycine (G) to Serine (S) at position 298 (G298S, p.Gly298Ser).
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 glycine (G) to small size and polar (S)
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:  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; also in irritable bowel syndrome; results in reduction of whole cell current density and a delay in channel activation kinetics without a change in single-channel conductance.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  298
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:   HKCVRNFTALNGTNGSVEAD  G LVWESLDLYLSDPENYLLKN
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                         HKCVRNFTALNGTNGSVEADGLVWESLDLYLSDPENYLLKN

Mouse                         HKCVRNFTELNGTNGSVEADGIVWNSLDVYLNDPANYLLKN

Rat                           HKCVRNFTELNGTNGSVEADGLVWNSLDVYLNDPANYLLKN

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.

TypePositionsDescription
Chain 1 – 2016 Sodium channel protein type 5 subunit alpha
Topological domain 273 – 357 Extracellular
Repeat 113 – 420 I
Glycosylation 283 – 283 N-linked (GlcNAc...) asparagine
Glycosylation 288 – 288 N-linked (GlcNAc...) asparagine
Glycosylation 291 – 291 N-linked (GlcNAc...) asparagine
Glycosylation 318 – 318 N-linked (GlcNAc...) asparagine
Disulfide bond 280 – 335


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;

Sodium channel mutation in irritable bowel syndrome: evidence for an ion channelopathy.
Saito Y.A.; Strege P.R.; Tester D.J.; Locke G.R. III; Talley N.J.; Bernard C.E.; Rae J.L.; Makielski J.C.; Ackerman M.J.; Farrugia G.;
Am. J. Physiol. 296:G211-G218(2009)
Cited for: VARIANT IRRITABLE BOWEL SYNDROME SER-298; CHARACTERIZATION OF VARIANT IRRITABLE BOWEL SYNDROME SER-298;

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.