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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q13936: Variant p.Arg858His

Voltage-dependent L-type calcium channel subunit alpha-1C
Gene: CACNA1C
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Variant information Variant position: help 858 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Arginine (R) to Histidine (H) at position 858 (R858H, p.Arg858His). 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: help Change from large size and basic (R) to medium size and polar (H) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 0 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: help In LQT8; gain-of-function effect on channel activity; slower inactivation. Any additional useful information about the variant.


Sequence information Variant position: help 858 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 2221 The length of the canonical sequence.
Location on the sequence: help PNPETTGEEDEEEPEMPVGP R PRPLSELHLKEKAVPMPEAS 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         PNPETTGEEDEEEPEMPVGPRPRPLSELHLKEKAVPMPEAS

Mouse                         SNPDTAGEEDEEEPEMPVGPRPRPLSELHLKEKAVPMPEAS

Rat                           SNPDTAGEEDEEEPEMPVGPRPRPLSELHLKEKAVPMPEAS

Rabbit                        PNPETTGEEDEEEPEMPVGPRPRPLSELHLKEKAVPMPEAS
Sequence annotation in neighborhood: help 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 – 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
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; TRANSPORTER ACTIVITY; Penetrance and expressivity of the R858H CACNA1C variant in a five-generation pedigree segregating an arrhythmogenic channelopathy.
Gardner R.J.M.; Crozier I.G.; Binfield A.L.; Love D.R.; Lehnert K.; Gibson K.; Lintott C.J.; Snell R.G.; Jacobsen J.C.; Jones P.P.; Waddell-Smith K.E.; Kennedy M.A.; Skinner J.R.;
Mol. Genet. Genomic Med. 7:E00476-E00476(2019)
Cited for: VARIANT LQT8 HIS-858;
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.