UniProtKB/Swiss-Prot P21817: Variant p.Gly248Arg

Ryanodine receptor 1
Gene: RYR1
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Variant information Variant position:

248 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 Glycine (G) to Arginine (R) at position 248 (G248R, p.Gly248Arg). 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 glycine (G) to large size and basic (R) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-2 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 MHS1; increases calcium-induced calcium release activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs1801086 [ dbSNP | Ensembl ]

Sequence information Variant position:

248 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

5038 The length of the canonical sequence.
Location on the sequence:

ECLTISPADSDDQRRLVYYE G GAVCTHARSLWRLEPLRISW 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                         ECLTISPADSDDQRRLVYYEGGAVCTHARSLWRLEPLRISW

Mouse                         ECLTISPSDSDDQRRLVYYEGGPVCTHARSLWRLEPLRISW

Rat                           ECLTISPSDSDDQRRLVYYEGGPVCTHARSLWRLEPLRISW

Pig                           ECLTISPADSDDQRRLVYYEGGSVCTHARSLWRLEPLRISW

Rabbit                        ECLTISAADSDDQRRLVYYEGGAVCTHARSLWRLEPLRISW

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 – 5038	Ryanodine receptor 1
Topological domain	1 – 4559	Cytoplasmic
Domain	210 – 264	MIR 3

Literature citations
Polymorphisms and deduced amino acid substitutions in the coding sequence of the ryanodine receptor (RYR1) gene in individuals with malignant hyperthermia.
Gillard E.F.; Otsu K.; Fujii J.; Duff C.L.; de Leon S.; Khanna V.K.; Britt B.A.; Worton R.G.; McLennan D.H.;
Genomics 13:1247-1254(1992)
Cited for: SEQUENCE REVISION TO 2324; 2840 AND 3380; INVOLVEMENT IN MHS1; VARIANTS MHS1 ARG-248 AND CYS-471; VARIANTS LEU-1787; CYS-2060 AND VAL-2550; North American malignant hyperthermia population: screening of the ryanodine receptor gene and identification of novel mutations.
Sambuughin N.; Sei Y.; Gallagher K.L.; Wyre H.W.; Madsen D.; Nelson T.E.; Fletcher J.E.; Rosenberg H.; Muldoon S.M.;
Anesthesiology 95:594-599(2001)
Cited for: VARIANTS MHS1 CYS-163; ARG-248; CYS-614; MET-2168; MET-2206; ILE-2214; THR-2367; ASN-2431; ARG-2434 AND HIS-2454; Malignant hyperthermia in North America: genetic screening of the three hot spots in the type I ryanodine receptor gene.
Sei Y.; Sambuughin N.N.; Davis E.J.; Sachs D.; Cuenca P.B.; Brandom B.W.; Tautz T.; Rosenberg H.; Nelson T.E.; Muldoon S.M.;
Anesthesiology 101:824-830(2004)
Cited for: VARIANTS MHS1 CYS-163; ARG-248; CYS-614; CYS-2163; MET-2168; MET-2206; ILE-2214; THR-2350; THR-2367; ASN-2431; ARG-2434; VAL-2437; HIS-2454 AND PRO-4824; Correlations between genotype and pharmacological, histological, functional, and clinical phenotypes in malignant hyperthermia susceptibility.
Monnier N.; Kozak-Ribbens G.; Krivosic-Horber R.; Nivoche Y.; Qi D.; Kraev N.; Loke J.; Sharma P.; Tegazzin V.; Figarella-Branger D.; Romero N.; Mezin P.; Bendahan D.; Payen J.-F.; Depret T.; Maclennan D.H.; Lunardi J.;
Hum. Mutat. 26:413-425(2005)
Cited for: VARIANTS MHS1 ARG-35; CYS-163; LEU-163; ARG-165; ASN-166; CYS-177; CYS-178; VAL-227; ARG-248; TRP-328; ARG-341; SER-401; HIS-401; MET-403; SER-522; TRP-552; CYS-614; LEU-614; CYS-2163; HIS-2163; MET-2168; MET-2206; ARG-2206; ASP-2344; MET-2346; THR-2350; THR-2428; ARG-2434; HIS-2435; CYS-2454; HIS-2454; CYS-2458; TRP-2676; SER-2787; MET-3916; SER-4684; GLN-4737; TRP-4737; ILE-4826; VAL-4838; ILE-4849; ARG-4876; GLU-4939 AND LEU-4973; CHARACTERIZATION OF VARIANTS MHS1 LEU-163; MET-2206; THR-2428; CYS-2454 AND HIS-2454; FUNCTION; TRANSPORTER ACTIVITY; ACTIVITY REGULATION; Ryanodine receptor type 1 gene variants in the malignant hyperthermia-susceptible population of the United States.
Brandom B.W.; Bina S.; Wong C.A.; Wallace T.; Visoiu M.; Isackson P.J.; Vladutiu G.D.; Sambuughin N.; Muldoon S.M.;
Anesth. Analg. 116:1078-1086(2013)
Cited for: VARIANTS MHS1 ALA-40; CYS-163; ARG-248; ARG-341; PRO-487; ALA-518; CYS-614; HIS-1043; LEU-1787; HIS-2163; MET-2206; HIS-2248; HIS-2351; MET-2354; LEU-2358; GLN-2383; ARG-2434; HIS-2454; ARG-3711; VAL-4178; ARG-4230; GLU-4837; HIS-4861 AND GLY-4906; VARIANTS CMYO1A TRP-975; MET-2168 AND GLY-3238; VARIANTS MET-974; LEU-1109; ARG-1393; CYS-2060 AND VAL-2321; Divergent activity profiles of type 1 ryanodine receptor channels carrying malignant hyperthermia and central core disease mutations in the amino-terminal Region.
Murayama T.; Kurebayashi N.; Yamazawa T.; Oyamada H.; Suzuki J.; Kanemaru K.; Oguchi K.; Iino M.; Sakurai T.;
PLoS ONE 10:E0130606-E0130606(2015)
Cited for: CHARACTERIZATION OF VARIANTS MHS1 ARG-35; CYS-163; LEU-163; ARG-248; ARG-341; CYS-401; HIS-401; SER-522; CYS-614 AND LEU-614; MUTAGENESIS OF TYR-522;

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.