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UniProtKB/Swiss-Prot Q99250: Variant p.Thr1420Met

Sodium channel protein type 2 subunit alpha
Gene: SCN2A
Chromosomal location: 2q23-q24
Variant information

Variant position:  1420
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 Threonine (T) to Methionine (M) at position 1420 (T1420M, p.Thr1420Met).
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 polar (T) to medium size and hydrophobic (M)
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

Variant description:  Probable disease-associated mutation found in a patient with autism spectrum disorder; decreased voltage-gated sodium channel activity; faster channel inactivation; fewer channels contribution to macroscopic currents and fewer channels expressed on membrane.
Any additional useful information about the variant.

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



Sequence information

Variant position:  1420
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  2005
The length of the canonical sequence.

Location on the sequence:   NVKVNFDNVGLGYLSLLQVA  T FKGWMDIMYAAVDSRNVELQ
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                         NVKVNFDNVGLGYLSLLQVATFKGWMDIMYAAVDSRNVELQ

Rat                           NVKVNFDNVGLGYLSLLQVATFKGWMDIMYAAVDSRNVELQ

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 – 2005 Sodium channel protein type 2 subunit alpha
Intramembrane 1409 – 1430 Pore-forming
Repeat 1190 – 1504 III


Literature citations

Opposing Effects on NaV1.2 Function Underlie Differences Between SCN2A Variants Observed in Individuals With Autism Spectrum Disorder or Infantile Seizures.
Ben-Shalom R.; Keeshen C.M.; Berrios K.N.; An J.Y.; Sanders S.J.; Bender K.J.;
Biol. Psychiatry 82:224-232(2017)
Cited for: VARIANTS ASN-12; GLY-82; HIS-379; CYS-937; HIS-937; 959-CYS--LYS-2005 DEL; 1013-GLY--LYS-2005 DEL; ARG-1386 AND MET-1420; CHARACTERIZATION OF VARIANTS ASN-12; GLY-82; HIS-379; CYS-937; HIS-937; 959-CYS--LYS-2005 DEL; 1013-GLY--LYS-2005 DEL; ARG-1386 AND MET-1420; INVOLVEMENT IN AUTISM SPECTRUM DISORDER; FUNCTION;

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.