UniProtKB/SwissProt variant VAR

Variant information

Variant position:

857

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 Proline (P) to Leucine (L) at position 857 (P857L, p.Pro857Leu).

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:

-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

Variant description:

In LQT8.

Any additional useful information about the variant.

Sequence information

Variant position:

857

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

Protein sequence length:

2221

The length of the canonical sequence.

Location on the sequence:

YPNPETTGEEDEEEPEMPVG P RPRPLSELHLKEKAVPMPEA

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                         YPNPETTGEEDEEEPEMPVGPRPRPLSELHLKEKAVPMPEA

Mouse                         HSNPDTAGEEDEEEPEMPVGPRPRPLSELHLKEKAVPMPEA

Rat                           HSNPDTAGEEDEEEPEMPVGPRPRPLSELHLKEKAVPMPEA

Rabbit                        YPNPETTGEEDEEEPEMPVGPRPRPLSELHLKEKAVPMPEA

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 – 2221	Voltage-dependent L-type calcium channel subunit alpha-1C
Topological domain	746 – 900	Cytoplasmic
Region	764 – 861	Disordered
Region	829 – 876	Interaction with STAC2

Literature citations

Exome sequencing and systems biology converge to identify novel mutations in the L-type calcium channel, CACNA1C, linked to autosomal dominant long QT syndrome.
Boczek N.J.; Best J.M.; Tester D.J.; Giudicessi J.R.; Middha S.; Evans J.M.; Kamp T.J.; Ackerman M.J.;
Circ. Cardiovasc. Genet. 6:279-289(2013)
Cited for: VARIANTS LQT8 GLU-834; ARG-857; LEU-857 AND GLN-1989; CHARACTERIZATION OF VARIANT LQT8 ARG-857; FUNCTION; INVOLVEMENT IN LQT8;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q13936: Variant p.Pro857Leu