UniProtKB/Swiss-Prot Q13936: Variant p.Pro381Ser

Voltage-dependent L-type calcium channel subunit alpha-1C
Gene: CACNA1C
Feedback?

Variant information Variant position:

381 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 Proline (P) to Serine (S) at position 381 (P381S, p.Pro381Ser). 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 (P) 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 LQT8; uncertain significance; no effect on channel activity. Any additional useful information about the variant.

Sequence information Variant position:

381 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:

TMEGWTDVLYWVNDAVGRDW P WIYFVTLIIIGSFFVLNLVL 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                         TMEGWTDVLYWVNDAVGRDWPWIYFVTLIIIGSFFVLNLVL

Mouse                         TMEGWTDVLYWMQDAMGYELPWVYFVSLVIFGSFFVLNLVL

Rat                           TMEGWTDVLYWMQDAMGYELPWVYFVSLVIFGSFFVLNLVL

Rabbit                        TMEGWTDVLYWMQDAMGYELPWVYFVSLVIFGSFFVLNLVL

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
Transmembrane	381 – 401	Helical; Name=S6 of repeat I
Repeat	111 – 408	I
Binding site	363 – 363
Site	363 – 363	Calcium ion selectivity and permeability
Alternative sequence	372 – 391	VNDAVGRDWPWIYFVTLIII -> MQDAMGYELPWVYFVSLVIF. In isoform 3, isoform 16, isoform 17, isoform 18, isoform 23, isoform 28, isoform 36 and isoform 37.
Mutagenesis	363 – 363	E -> K. Loss of selectivity for divalent over monovalent cations.
Helix	381 – 412

Literature citations
Long QT syndrome type 8: novel CACNA1C mutations causing QT prolongation and variant phenotypes.
Fukuyama M.; Wang Q.; Kato K.; Ohno S.; Ding W.G.; Toyoda F.; Itoh H.; Kimura H.; Makiyama T.; Ito M.; Matsuura H.; Horie M.;
Europace 16:1828-1837(2014)
Cited for: VARIANTS LQT8 SER-381; ILE-456; ASP-582; HIS-858 AND CYS-1831; CHARACTERIZATION OF VARIANTS LQT8 SER-381; ILE-456; ASP-582; HIS-858 AND CYS-1831; FUNCTION; SUBUNIT; SUBCELLULAR LOCATION; INTERACTION WITH CACNB2 AND CACNA2D1;

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.