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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P35499: Variant p.Arg1448Cys

Sodium channel protein type 4 subunit alpha
Gene: SCN4A
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Variant information Variant position: help 1448 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] 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: help From Arginine (R) to Cysteine (C) at position 1448 (R1448C, p.Arg1448Cys). 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: help 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: help -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: help In PMC; changes the voltage-gated sodium channel activity; increases membrane hyperexcitability at low temperature; decreases channel activation, deactivation, fast inactivation and recovery delay from fast inactivation. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 1448 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1836 The length of the canonical sequence.
Location on the sequence: help IVGLALSDLIQKYFVSPTLF R VIRLARIGRVLRLIRGAKGI 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         IVGLALSDLIQKYFVSPTLFRVIRLARIGRVLRLIRGAKGI

Mouse                         IVGLALSDLIQKYFVSPTLFRVIRLARIGRVLRLIRGAKGI

Rat                           IVGLALSDLIQKYFVSPTLFRVIRLARIGRVLRLIRGAKGI

Horse                         IVGLALSDLIQKYFVSPTLFRVIRLARIGRVLRLIRGAKGI
Sequence annotation in neighborhood: help 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 – 1836 Sodium channel protein type 4 subunit alpha
Transmembrane 1446 – 1462 Helical; Name=S4 of repeat IV
Repeat 1335 – 1633 IV
Helix 1447 – 1450



Literature citations
Mutations in an S4 segment of the adult skeletal muscle sodium channel cause paramyotonia congenita.
Ptacek L.J.; George A.L. Jr.; Barchi R.L.; Griggs R.C.; Riggs J.E.; Robertson M.; Leppert M.F.;
Neuron 8:891-897(1992)
Cited for: VARIANTS PMC CYS-1448 AND HIS-1448; Temperature-sensitive defects in paramyotonia congenita mutants R1448C and T1313M.
Dice M.S.; Abbruzzese J.L.; Wheeler J.T.; Groome J.R.; Fujimoto E.; Ruben P.C.;
Muscle Nerve 30:277-288(2004)
Cited for: VARIANTS PMC MET-1313 AND CYS-1448; CHARACTERIZATION OF VARIANTS PMC MET-1313 AND CYS-1448; FUNCTION; TRANSPORTER ACTIVITY; SUBCELLULAR LOCATION; What causes paramyotonia in the United Kingdom? Common and new SCN4A mutations revealed.
Matthews E.; Tan S.V.; Fialho D.; Sweeney M.G.; Sud R.; Haworth A.; Stanley E.; Cea G.; Davis M.B.; Hanna M.G.;
Neurology 70:50-53(2008)
Cited for: VARIANTS PMC LYS-270; MET-704; ALA-1306; GLU-1306; MET-1313; PRO-1436; CYS-1448; HIS-1448; LEU-1448; GLU-1456; SER-1473 AND MET-1589;
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.