UniProtKB/Swiss-Prot O95180: Variant p.Cys456Ser

Voltage-dependent T-type calcium channel subunit alpha-1H
Gene: CACNA1H
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Variant information Variant position:

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

US 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 Cysteine (C) to Serine (S) at position 456 (C456S, p.Cys456Ser). 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 (C) to small size and polar (S) 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 ECA6; uncertain significance; results in increased T-current amplitude and lower threshold for spikes generation; results in increased neuronal excitability. Any additional useful information about the variant.

Sequence information Variant position:

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

2353 The length of the canonical sequence.
Location on the sequence:

QRARHLSNDSTLASFSEPGS C YEELLKYVGHIFRKVKRRSL 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                         QRARHLSNDSTLASFSEPGSCYEELLKYVGHIFRKVKRRSL

Mouse                         QRARYLSNDSTLASFSEPGSCYEELLKYVGHIFRKVKRRSL

Rat                           QRARYLSNDSTLASFSEPGSCYEELLKYVGHIFRKVKRRSL

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 – 2353	Voltage-dependent T-type calcium channel subunit alpha-1H
Topological domain	420 – 793	Cytoplasmic

Literature citations
Association between genetic variation of CACNA1H and childhood absence epilepsy.
Chen Y.; Lu J.; Pan H.; Zhang Y.; Wu H.; Xu K.; Liu X.; Jiang Y.; Bao X.; Yao Z.; Ding K.; Lo W.H.; Qiang B.; Chan P.; Shen Y.; Wu X.;
Ann. Neurol. 54:239-243(2003)
Cited for: VARIANTS ECA6 LEU-161; LYS-282; SER-456; SER-499; LEU-648; GLN-744; VAL-748; ASP-773; SER-784; MET-831; SER-848 AND ASN-1463; VARIANTS VAL-313; LEU-640; ALA-664; SER-684; CYS-788; HIS-2060; HIS-2077 AND SER-2173; Mechanisms by which a CACNA1H mutation in epilepsy patients increases seizure susceptibility.
Eckle V.S.; Shcheglovitov A.; Vitko I.; Dey D.; Yap C.C.; Winckler B.; Perez-Reyes E.;
J. Physiol. (Lond.) 592:795-809(2014)
Cited for: CHARACTERIZATION OF VARIANT ECA6 SER-456; FUNCTION; TRANSPORTER ACTIVITY;

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.