UniProtKB/Swiss-Prot Q13936: Variant p.Glu477Lys

Voltage-dependent L-type calcium channel subunit alpha-1C
Gene: CACNA1C
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Variant information Variant position:

477 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 Glutamate (E) to Lysine (K) at position 477 (E477K, p.Glu477Lys). 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 acidic (E) to large size and basic (K) 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. Any additional useful information about the variant.

Sequence information Variant position:

477 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:

DEEKPRNMSMPTSETESVNT E NVAGGDIEGENCGARLAHRI 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                         DEEKPRNMSMPTSETESVNTENVAGGDIEGENCGARLAHRI

Mouse                         DEDKPRNMSMPTSETESVNTENVAGGDIEGENCGARLAHRI

Rat                           DEDKPRNMSMPTSETESVNTENVAGGDIEGENCGARLAHRI

Rabbit                        DEEKPRNMSMPTSETESVNTENVAGGDIEGENCGARLAHRI

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	402 – 524	Cytoplasmic
Region	449 – 481	Disordered
Compositional bias	465 – 478	Polar residues
Modified residue	469 – 469	Phosphoserine
Modified residue	476 – 476	Phosphothreonine

Literature citations
Gain-of-function mutations in the calcium channel CACNA1C (Cav1.2) cause non-syndromic long-QT but not Timothy syndrome.
Wemhoener K.; Friedrich C.; Stallmeyer B.; Coffey A.J.; Grace A.; Zumhagen S.; Seebohm G.; Ortiz-Bonnin B.; Rinne S.; Sachse F.B.; Schulze-Bahr E.; Decher N.;
J. Mol. Cell. Cardiol. 80:186-195(2015)
Cited for: VARIANTS LQT8 THR-28; LYS-477; GLY-860; THR-1186; VAL-1186; THR-1365; MET-1523; LYS-1544; ASN-1787; ILE-1800; LYS-1948; MET-1953; ASN-2081; ILE-2097 AND GLY-2122; CHARACTERIZATION OF VARIANTS LQT8 THR-28; GLY-860; THR-1186; VAL-1186; MET-1523 AND LYS-1544; VARIANTS ARG-37; THR-304; SER-817; ILE-1755; GLY-1765; MET-1835; ARG-1843; CYS-1972; GLN-2056 AND SER-2174; 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.