UniProtKB/Swiss-Prot P35498: Variant p.Arg393His

Sodium channel protein type 1 subunit alpha
Gene: SCN1A
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Variant information Variant position:

393 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

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:

From Arginine (R) to Histidine (H) at position 393 (R393H, p.Arg393His). 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
Variant description:

In DRVT and ICEGTC; results in a non-functional channel. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs121917927 [ dbSNP | Ensembl ]

Sequence information Variant position:

393 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

2009 The length of the canonical sequence.
Location on the sequence:

LSLFRLMTQDFWENLYQLTL R AAGKTYMIFFVLVIFLGSFY 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                         LSLFRLMTQDFWENLYQLTLRAAGKTYMIFFVLVIFLGSFY

Mouse                         LSLFRLMTQDFWENLYQLTLRAAGKTYMIFFVLVIFLGSFY

Rat                           LSLFRLMTQDFWENLYQLTLRAAGKTYMIFFVLVIFLGSFY

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 – 2009	Sodium channel protein type 1 subunit alpha
Topological domain	393 – 399	Extracellular
Repeat	110 – 454	I
Helix	384 – 395

Literature citations
De novo SCN1A mutations are a major cause of severe myoclonic epilepsy of infancy.
Claes L.; Ceulemans B.; Audenaert D.; Smets K.; Loefgren A.; Del-Favero J.; Ala-Mello S.; Basel-Vanagaite L.; Plecko B.; Raskin S.; Thiry P.; Wolf N.I.; Van Broeckhoven C.; De Jonghe P.;
Hum. Mutat. 21:615-621(2003)
Cited for: VARIANTS DRVT HIS-393; GLN-939; ARG-959; ARG-1434; SER-1661 AND GLU-1749; Nonfunctional SCN1A is common in severe myoclonic epilepsy of infancy.
Ohmori I.; Kahlig K.M.; Rhodes T.H.; Wang D.W.; George A.L. Jr.;
Epilepsia 47:1636-1642(2006)
Cited for: CHARACTERIZATION OF VARIANTS DRVT GLU-177; SER-227; HIS-393; ASN-426; GLN-939; ARG-959; PHE-1289 DEL AND ILE-1909; Idiopathic epilepsies with seizures precipitated by fever and SCN1A abnormalities.
Marini C.; Mei D.; Temudo T.; Ferrari A.R.; Buti D.; Dravet C.; Dias A.I.; Moreira A.; Calado E.; Seri S.; Neville B.; Narbona J.; Reid E.; Michelucci R.; Sicca F.; Cross H.J.; Guerrini R.;
Epilepsia 48:1678-1685(2007)
Cited for: VARIANTS DRVT GLN-101; ILE-322; GLY-356; THR-358; CYS-393; HIS-393; LEU-957; TYR-1414; TRP-1470; ARG-1588; TYR-1608; MET-1630; ARG-1658; ARG-1716; VAL-1783 AND LYS-1787; VARIANTS GEFSP2 PRO-74; ARG-1204 AND SER-1687; Analysis of SCN1A mutation and parental origin in patients with Dravet syndrome.
Sun H.; Zhang Y.; Liu X.; Ma X.; Yang Z.; Qin J.; Jiang Y.; Qi Y.; Wu X.;
J. Hum. Genet. 55:421-427(2010)
Cited for: VARIANTS DRVT SER-90; THR-91; TRP-101; GLN-101; THR-239; ARG-259; HIS-393; TYR-939; GLY-952; LYS-1210; PRO-1260; PRO-1287; MET-1335; MET-1390; GLU-1433; GLU-1586 AND THR-1783; Genotype-phenotype associations in SCN1A-related epilepsies.
Zuberi S.M.; Brunklaus A.; Birch R.; Reavey E.; Duncan J.; Forbes G.H.;
Neurology 76:594-600(2011)
Cited for: VARIANTS DRVT PHE-17 DEL; THR-68; ASN-79; CYS-84; PRO-98; GLN-101; TRP-101; ARG-108; ASP-127; ARG-199; SER-227; THR-227; SER-232; ARG-233; VAL-342; ASP-343; TRP-351; SER-359; ARG-363; ARG-384; CYS-393; HIS-393; VAL-400; VAL-403; PHE-406; GLY-626; ASP-762; THR-785; ILE-812; ARG-842; 854-GLY-LEU-855 DEL; CYS-859; GLN-862; PRO-890; CYS-932; PRO-933; CYS-946; HIS-946; ARG-950; LYS-954; LYS-956; LEU-957; ILE-976; VAL-979; ARG-993; 999-ASN-LEU-1000 DELINS LEU-ILE-SER; LYS-1208; LYS-1221; PHE-1230; ASP-1238; ALA-1266; ASN-1288; VAL-1320; PRO-1326; GLY-1350; ARG-1358; PRO-1370; HIS-1378; THR-1378; ILE-1394; TYR-1396; SER-1417; PHE-1423; ALA-1429 DEL; VAL-1433; LYS-1450; SER-1451; LYS-1454; HIS-1462; LYS-1476; LYS-1503; GLY-1544; GLU-1586; ARG-1588; HIS-1592; PRO-1592; SER-1605; GLU-1637; THR-1638; CYS-1648; GLU-1653; PRO-1660; PRO-1667; LEU-1668; ILE-1672; THR-1673; THR-1683; ASP-1684; TRP-1688; ARG-1714; ASN-1763; ASN-1770; PHE-1770; THR-1770; THR-1780; VAL-1783; LYS-1787; PRO-1832; LYS-1852; LEU-1855; GLU-1880; THR-1909 DEL AND ARG-1927 DELINS ILE-ILE-GLN; VARIANTS GEFSP2 LEU-218; ILE-254; GLY-291; THR-960; VAL-973; SER-1204; PHE-1230; ASP-1414; HIS-1596; LEU-1739 AND THR-1867; VARIANTS ASN-45; VAL-333; ASN-382; HIS-604; ILE-699; THR-924; HIS-931; GLU-1006; ILE-1079; THR-1109; ASP-1308; ASP-1326; MET-1483 AND PHE-1683; Targeted next generation sequencing as a diagnostic tool in epileptic disorders.
Lemke J.R.; Riesch E.; Scheurenbrand T.; Schubach M.; Wilhelm C.; Steiner I.; Hansen J.; Courage C.; Gallati S.; Buerki S.; Strozzi S.; Simonetti B.G.; Grunt S.; Steinlin M.; Alber M.; Wolff M.; Klopstock T.; Prott E.C.; Lorenz R.; Spaich C.; Rona S.; Lakshminarasimhan M.; Kroell J.; Dorn T.; Kraemer G.; Synofzik M.; Becker F.; Weber Y.G.; Lerche H.; Boehm D.; Biskup S.;
Epilepsia 53:1387-1398(2012)
Cited for: VARIANTS DRVT VAL-289; ARG-379 AND HIS-393; Prevalence of SCN1A mutations in children with suspected Dravet syndrome and intractable childhood epilepsy.
Wang J.W.; Shi X.Y.; Kurahashi H.; Hwang S.K.; Ishii A.; Higurashi N.; Kaneko S.; Hirose S.;
Epilepsy Res. 102:195-200(2012)
Cited for: VARIANTS DRVT CYS-84; GLN-101; TRP-101; ILE-105; ARG-179; ARG-190; ARG-226; SER-227; ARG-259; ARG-280; ALA-281; PRO-363; ARG-384; HIS-393; TRP-409; CYS-426; MET-875; ILE-876; PHE-896; ILE-934; PHE-940; CYS-946; HIS-946; LEU-987; GLY-1316; VAL-1339; MET-1344; PRO-1355; VAL-1385; GLY-1418; PRO-1427; CYS-1453; HIS-1462; SER-1472; TYR-1485; GLU-1503 DEL; LYS-1503; VAL-1545; ARG-1555; GLY-1608; LEU-1630; ASN-1638; SER-1642; VAL-1662; PRO-1667; PHE-1677; THR-1683; SER-1692; CYS-1694; GLY-1727; ARG-1741; PHE-1766 DEL; PHE-1771; THR-1783; VAL-1783 AND THR-1792; VARIANTS ICEGTC SER-90; GLN-101; SER-178; MET-252; ARG-290; HIS-393; ILE-896; ALA-944; GLN-1213; CYS-1254; THR-1325; PRO-1328; LEU-1357; ARG-1376; ASP-1429; HIS-1462; LYS-1511; VAL-1619; SER-1684; PRO-1724; CYS-1781 AND TRP-1861; VARIANTS GLN-542 AND CYS-1575; A mutation in GABRB3 associated with Dravet syndrome.
Le S.V.; Le P.H.T.; Le T.K.V.; Kieu Huynh T.T.; Hang Do T.T.;
Am. J. Med. Genet. A 173:2126-2131(2017)
Cited for: VARIANT DRVT HIS-393;

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.