UniProtKB/SwissProt variant VAR

Variant information

Variant position:

136

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 Methionine (M) to Isoleucine (I) at position 136 (M136I, p.Met136Ile).

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:

Similar physico-chemical property. Both residues are medium size and hydrophobic.

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:

In DEE11; responds to ketogenic diet.

Any additional useful information about the variant.

Sequence information

Variant position:

136

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:

NPIRKLAIKILVHSLFNMLI M CTILTNCVFMTMSNPPDWTK

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                         NPIRKLAIKILVHSLFNMLIMCTILTNCVFMTMSNPPDWTK

Mouse                         NPIRKLAIKILVHSLFNVLIMCTILTNCVFMTMSNPPDWTK

Rat                           NPIRKLAIKILVHSLFNVLIMCTILTNCVFMTMSNPPDWTK

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 – 2005	Sodium channel protein type 2 subunit alpha
Transmembrane	130 – 148	Helical; Name=S1 of repeat I
Repeat	111 – 456	I
Helix	129 – 145

Literature citations

Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.
Carvill G.L.; Heavin S.B.; Yendle S.C.; McMahon J.M.; O'Roak B.J.; Cook J.; Khan A.; Dorschner M.O.; Weaver M.; Calvert S.; Malone S.; Wallace G.; Stanley T.; Bye A.M.; Bleasel A.; Howell K.B.; Kivity S.; Mackay M.T.; Rodriguez-Casero V.; Webster R.; Korczyn A.; Afawi Z.; Zelnick N.; Lerman-Sagie T.; Lev D.; Moeller R.S.; Gill D.; Andrade D.M.; Freeman J.L.; Sadleir L.G.; Shendure J.; Berkovic S.F.; Scheffer I.E.; Mefford H.C.;
Nat. Genet. 45:825-830(2013)
Cited for: VARIANTS DEE11 ILE-136; ASN-905; CYS-928 AND GLN-1882;

SCN2A encephalopathy: A major cause of epilepsy of infancy with migrating focal seizures.
Howell K.B.; McMahon J.M.; Carvill G.L.; Tambunan D.; Mackay M.T.; Rodriguez-Casero V.; Webster R.; Clark D.; Freeman J.L.; Calvert S.; Olson H.E.; Mandelstam S.; Poduri A.; Mefford H.C.; Harvey A.S.; Scheffer I.E.;
Neurology 85:958-966(2015)
Cited for: VARIANTS DEE11 ILE-136; LYS-218; LEU-856; ASN-905; CYS-928; ARG-1593; VAL-1634 AND GLN-1882; VARIANT BFIS3 SER-240; VARIANT LYS-976;

Ketogenic diet as a successful early treatment modality for SCN2A mutation.
Turkdogan D.; Thomas G.; Demirel B.;
Brain Dev. 41:389-391(2019)
Cited for: VARIANT DEE11 ILE-136;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q99250: Variant p.Met136Ile