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UniProtKB/Swiss-Prot P21579: Variant p.Ile368Thr

Synaptotagmin-1
Gene: SYT1
Variant information

Variant position:  368
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 Isoleucine (I) to Threonine (T) at position 368 (I368T, p.Ile368Thr).
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 hydrophobic (I) to medium size and polar (T)
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

Involvement in disease:  Baker-Gordon syndrome (BAGOS) [MIM:618218]: An autosomal dominant neurodevelopmental disorder characterized by infantile hypotonia, congenital ophthalmic abnormalities, involuntary and hyperkinetic movements, stereotypic behavior, poor or absent speech, EEG abnormalities, and global developmental delay varying in severity from moderate to profound. Behavioral characteristics include sleep disturbance and episodic agitation. {ECO:0000269|PubMed:25705886, ECO:0000269|PubMed:25712080, ECO:0000269|PubMed:30107533}. 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 BAGOS.
Any additional useful information about the variant.

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



Sequence information

Variant position:  368
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  422
The length of the canonical sequence.

Location on the sequence:   VPFEQIQKVQVVVTVLDYDK  I GKNDAIGKVFVGYNSTGAEL
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                         VPFEQIQKVQVVVTVLDY-------------------------------------------------------------DKIGKNDA--------------------------------IGKV---------------FVGYNSTGAEL

Mouse                         VPFEQIQKVQVVVTVLDY-----------------------

Rat                           VPFEQIQKVQVVVTVLDY-----------------------

Bovine                        VPFEQIQKVQVVVTVLDY-----------------------

Chicken                       VPFEQIQKVQIVVTVLDY-----------------------

Caenorhabditis elegans        VPFEQIQKVSLMITVMDY-----------------------

Baker's yeast                 RERDSLGKSHFASLVLAYTEHHSTGSHTSNTTAASSSAKHN

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 – 422 Synaptotagmin-1
Topological domain 81 – 422 Cytoplasmic
Domain 273 – 406 C2 2
Region 136 – 382 Phospholipid binding
Metal binding 364 – 364 Calcium 4
Metal binding 364 – 364 Calcium 5
Metal binding 366 – 366 Calcium 4
Metal binding 366 – 366 Calcium 5
Metal binding 372 – 372 Calcium 5
Beta strand 367 – 369


Literature citations

Identification of a human synaptotagmin-1 mutation that perturbs synaptic vesicle cycling.
Baker K.; Gordon S.L.; Grozeva D.; van Kogelenberg M.; Roberts N.Y.; Pike M.; Blair E.; Hurles M.E.; Chong W.K.; Baldeweg T.; Kurian M.A.; Boyd S.G.; Cousin M.A.; Raymond F.L.;
J. Clin. Invest. 125:1670-1678(2015)
Cited for: INVOLVEMENT IN BAGOS; VARIANT BAGOS THR-368;

SYT1-associated neurodevelopmental disorder: a case series.
Baker K.; Gordon S.L.; Melland H.; Bumbak F.; Scott D.J.; Jiang T.J.; Owen D.; Turner B.J.; Boyd S.G.; Rossi M.; Al-Raqad M.; Elpeleg O.; Peck D.; Mancini G.M.S.; Wilke M.; Zollino M.; Marangi G.; Weigand H.; Borggraefe I.; Haack T.; Stark Z.; Sadedin S.; Tan T.Y.; Jiang Y.; Gibbs R.A.; Ellingwood S.; Amaral M.; Kelley W.; Kurian M.A.; Cousin M.A.; Raymond F.L.;
Brain 141:2576-2591(2018)
Cited for: INVOLVEMENT IN BAGOS; VARIANTS BAGOS LYS-303; GLY-304; GLU-366; THR-368 AND LYS-371; CHARACTERIZATION OF VARIANTS BAGOS LYS-303; GLY-304; GLU-366; THR-368 AND LYS-371;

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.