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UniProtKB/Swiss-Prot P35498: Variant p.Trp190Arg

Sodium channel protein type 1 subunit alpha
Gene: SCN1A
Chromosomal location: 2q24.3
Variant information

Variant position:  190
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 Tryptophan (W) to Arginine (R) at position 190 (W190R, p.Trp190Arg).
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 aromatic (W) to large size and basic (R)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -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

Involvement in disease:  Epileptic encephalopathy, early infantile, 6 (EIEE6) [MIM:607208]: A severe form of epileptic encephalopathy characterized by generalized tonic, clonic, and tonic-clonic seizures that are initially induced by fever and begin during the first year of life. Later, patients also manifest other seizure types, including absence, myoclonic, and simple and complex partial seizures. Psychomotor development delay is observed around the second year of life. Some patients manifest a borderline disease phenotype and do not necessarily fulfill all diagnostic criteria for core EIEE6. EIEE6 is considered to be the most severe phenotype within the spectrum of generalized epilepsies with febrile seizures-plus. {ECO:0000269|PubMed:11359211, ECO:0000269|PubMed:12083760, ECO:0000269|PubMed:12566275, ECO:0000269|PubMed:12754708, ECO:0000269|PubMed:12821740, ECO:0000269|PubMed:14504318, ECO:0000269|PubMed:14672992, ECO:0000269|PubMed:14738421, ECO:0000269|PubMed:15087100, ECO:0000269|PubMed:15944908, ECO:0000269|PubMed:16122630, ECO:0000269|PubMed:16458823, ECO:0000269|PubMed:16713920, ECO:0000269|PubMed:17054684, ECO:0000269|PubMed:17054685, ECO:0000269|PubMed:17129991, ECO:0000269|PubMed:17347258, ECO:0000269|PubMed:17561957, ECO:0000269|PubMed:18413471, ECO:0000269|PubMed:18639757, ECO:0000269|PubMed:18930999, ECO:0000269|PubMed:19522081, ECO:0000269|PubMed:19563458, ECO:0000269|PubMed:19589774, ECO:0000269|PubMed:19783390, ECO:0000269|PubMed:20110217, ECO:0000269|PubMed:20431604, ECO:0000269|PubMed:20452746, ECO:0000269|PubMed:20522430, ECO:0000269|PubMed:20729507, ECO:0000269|PubMed:21248271, ECO:0000269|PubMed:21864321, ECO:0000269|PubMed:22092154, ECO:0000269|PubMed:22612257, ECO:0000269|PubMed:23195492, ECO:0000269|PubMed:23662938, ECO:0000269|PubMed:23708187, ECO:0000269|PubMed:25818041, ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:27864847, ECO:0000269|PubMed:28544625}. 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 EIEE6.
Any additional useful information about the variant.

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



Sequence information

Variant position:  190
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:   LIKIIARGFCLEDFTFLRDP  W NWLDFTVITFAYVTEFVDLG
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                         LIKIIARGFCLEDFTFLRDPWNWLDFTVITFAYVTEFVDLG

Mouse                         LIKIIARGFCLEDFTFLRDPWNWLDFTVITFAYVTEFVDLG

Rat                           LIKIIARGFCLEDFTFLRDPWNWLDFTVITFAYVTEFVDLG

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 – 2009 Sodium channel protein type 1 subunit alpha
Transmembrane 190 – 207 Helical; Name=S3 of repeat I
Repeat 110 – 454 I


Literature citations

Mutations of neuronal voltage-gated Na+ channel alpha 1 subunit gene SCN1A in core severe myoclonic epilepsy in infancy (SMEI) and in borderline SMEI (SMEB).
Fukuma G.; Oguni H.; Shirasaka Y.; Watanabe K.; Miyajima T.; Yasumoto S.; Ohfu M.; Inoue T.; Watanachai A.; Kira R.; Matsuo M.; Muranaka H.; Sofue F.; Zhang B.; Kaneko S.; Mitsudome A.; Hirose S.;
Epilepsia 45:140-148(2004)
Cited for: VARIANTS EIEE6 GLN-101; ARG-190; ILE-934; ALA-944; CYS-946; HIS-946; PRO-1355; MET-1559 DEL; SER-1692; CYS-1694; PHE-1766 DEL AND CYS-1781;

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 EIEE6 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;

Diagnostic targeted resequencing in 349 patients with drug-resistant pediatric epilepsies identifies causative mutations in 30 different genes.
Parrini E.; Marini C.; Mei D.; Galuppi A.; Cellini E.; Pucatti D.; Chiti L.; Rutigliano D.; Bianchini C.; Virdo S.; De Vita D.; Bigoni S.; Barba C.; Mari F.; Montomoli M.; Pisano T.; Rosati A.; Guerrini R.;
Hum. Mutat. 38:216-225(2017)
Cited for: VARIANTS EIEE6 ARG-190; PRO-228; ILE-1605 AND GLN-1645; VARIANT ASP-616;

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.