UniProtKB/Swiss-Prot P21817: Variant p.Val2168Met

Ryanodine receptor 1
Gene: RYR1
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Variant information Variant position:

2168 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 Valine (V) to Methionine (M) at position 2168 (V2168M, p.Val2168Met). 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:

Similar physico-chemical property. Both residues are medium size and hydrophobic. 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 CMYO1A and MHS1; no difference in the thapsigargin-sensitive calcium stores of cells carrying this mutation and the wild-type; increases calcium-induced calcium release activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs118192176 [ dbSNP | Ensembl ]

Sequence information Variant position:

2168 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:

SVEDTMSLLECLGQIRSLLI V QMGPQEENLMIQSIGNIMNN 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                         SVEDTMSLLECLGQIRSLLIVQMGPQEENLMIQSIGNIMNN

Mouse                         SVEDTMSLLECLGQIRSLLIVQMGPQEENLMIQSIGNIMNN

Rat                           SVEDTMSLLECLGQIRSLLIVQMGPQEENLMIQSIGNIMNN

Pig                           SVEDTMSLLECLGQIRSLLIVQMGPQEENLMIQSIGNIMNN

Rabbit                        SVEDTMSLLECLGQIRSLLIVQMGPQEENLMIQSIGNIMNN

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
Region	841 – 2959	6 X approximate repeats

Literature citations
Identification of novel mutations in the ryanodine-receptor gene (RYR1) in malignant hyperthermia: genotype-phenotype correlation.
Manning B.M.; Quane K.A.; Ording H.; Urwyler A.; Tegazzin V.; Lehane M.; O'Halloran J.; Hartung E.; Giblin L.M.; Lynch P.J.; Vaughan P.; Censier K.; Bendixen D.; Comi G.P.; Heytens L.; Monsieurs K.; Fagerlund T.H.; Wolz W.; Heffron J.J.A.; Mueller C.R.; McCarthy T.V.;
Am. J. Hum. Genet. 62:599-609(1998)
Cited for: VARIANTS MHS1 CYS-2163; MET-2168 AND MET-2206; VARIANT CMYO1A HIS-2163; 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; Familial and sporadic forms of central core disease are associated with mutations in the C-terminal domain of the skeletal muscle ryanodine receptor.
Monnier N.; Romero N.B.; Lerale J.; Landrieu P.; Nivoche Y.; Fardeau M.; Lunardi J.;
Hum. Mol. Genet. 10:2581-2592(2001)
Cited for: VARIANTS CMYO1A MET-2168; 4214-ARG--PHE-4216 DEL; 4647-LEU-SER-4648 DEL; PRO-4793; CYS-4796; CYS-4825; PHE-4860 DEL; HIS-4861; TRP-4893; THR-4898; GLU-4899 AND GLY-4914; Identification of four novel mutations in the C-terminal membrane spanning domain of the ryanodine receptor 1: association with central core disease and alteration of calcium homeostasis.
Tilgen N.; Zorzato F.; Halliger-Keller B.; Muntoni F.; Sewry C.; Palmucci L.M.; Schneider C.; Hauser E.; Lehmann-Horn F.; Mueller C.R.; Treves S.;
Hum. Mol. Genet. 10:2879-2887(2001)
Cited for: VARIANTS CMYO1A HIS-4861; ARG-4891; THR-4898; ARG-4899 AND VAL-4906; CHARACTERIZATION OF VARIANTS CMYO1A MET-2168; HIS-4861; TRP-4893; THR-4898 AND ARG-4899; FUNCTION; TRANSPORTER ACTIVITY; Mutation screening in the ryanodine receptor 1 gene (RYR1) in patients susceptible to malignant hyperthermia who show definite IVCT results: identification of three novel mutations.
Rueffert H.; Olthoff D.; Deutrich C.; Meinecke C.D.; Froster U.G.;
Acta Anaesthesiol. Scand. 46:692-698(2002)
Cited for: VARIANTS MHS1 CYS-163; ASN-166; ARG-341; HIS-401; CYS-614; GLU-2129; MET-2168; MET-2206; THR-2428; ARG-2434; HIS-2435; TRP-2452 AND HIS-2454; Scanning for mutations of the ryanodine receptor (RYR1) gene by denaturing HPLC: detection of three novel malignant hyperthermia alleles.
Tammaro A.; Bracco A.; Cozzolino S.; Esposito M.; Di Martino A.; Savoia G.; Zeuli L.; Piluso G.; Aurino S.; Nigro V.;
Clin. Chem. 49:761-768(2003)
Cited for: VARIANTS MHS1 CYS-44; CYS-533; LEU-2117; PRO-2163; MET-2168; LEU-2435 AND HIS-2454; VARIANT LYS-2101; 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; MET-3916; SER-4684; GLN-4737; TRP-4737; ILE-4826; VAL-4838; ILE-4849; ARG-4876; GLU-4939 AND LEU-4973; VARIANTS TRP-2676 AND SER-2787; 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; 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; LEU-1787; CYS-2060 AND VAL-2321; 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 CMYO1A 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.