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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P21817: Variant p.Arg2458His

Ryanodine receptor 1
Gene: RYR1
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Variant information Variant position: help 2458 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 2458 (R2458H, p.Arg2458His). 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 MHS1. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 2458 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 5038 The length of the canonical sequence.
Location on the sequence: help PEMHLIQAGKGEALRIRAIL R SLVPLEDLVGIISLPLQIPT 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                         PEMHLIQAGKGEALRIRAILRSLVPLEDLVGIISLPLQIPT

Mouse                         PETHLIQAGKGEALRIRAILRSLVPLDDLVGIISLPLQIPT

Rat                           PEMHLIQAGKGEALRIRAILRSLVPLDDLVGIISLPLQIPT

Pig                           PEMHLIQAGKGEALRIRAILRSLVPLDDLVGIISLPLQIPT

Rabbit                        PEMHLIQAGKGEALRIRAILRSLVPLDDLVGIISLPLQIPT

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 – 5038 Ryanodine receptor 1
Topological domain 1 – 4559 Cytoplasmic
Region 841 – 2959 6 X approximate repeats



Literature citations
Novel mutations at a CpG dinucleotide in the ryanodine receptor in malignant hyperthermia.
Manning B.M.; Quane K.A.; Lynch P.J.; Urwyler A.; Tegazzin V.; Krivosic-Horber R.; Censier K.; Comi G.P.; Adnet P.; Wolz W.; Lunardi J.; Muller C.R.; McCarthy T.V.;
Hum. Mutat. 11:45-50(1998)
Cited for: VARIANTS MHS1 CYS-2458 AND HIS-2458; RYR1 mutations in UK central core disease patients: more than just the C-terminal transmembrane region of the RYR1 gene.
Shepherd S.; Ellis F.; Halsall J.; Hopkins P.; Robinson R.;
J. Med. Genet. 41:E33-E33(2004)
Cited for: VARIANTS CMYP1A GLY-160; ASP-4638; PHE-4814; HIS-4861 AND MET-4938; VARIANTS MHS1 CYS-614; MET-2346; GLY-2348; TRP-2452; HIS-2458; PRO-4824 AND GLU-4939; Genotype-phenotype correlations of malignant hyperthermia and central core disease mutations in the central region of the RYR1 channel.
Murayama T.; Kurebayashi N.; Ogawa H.; Yamazawa T.; Oyamada H.; Suzuki J.; Kanemaru K.; Oguchi K.; Iino M.; Sakurai T.;
Hum. Mutat. 37:1231-1241(2016)
Cited for: CHARACTERIZATION OF VARIANTS MHS1 CYS-2163; HIS-2163; MET-2168; MET-2206; THR-2350; ARG-2434; HIS-2435; CYS-2454; HIS-2454; CYS-2458; HIS-2458 AND HIS-2508; CHARACTERIZATION OF VARIANT CMYP1A CYS-2508; CHARACTERIZATION OF VARIANT ALA-2375 AND HIS-2508; 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.