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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P0DP23: Variant p.Asn54Ile

Calmodulin-1
Gene: CALM1
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Variant information Variant position: help 54 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 Asparagine (N) to Isoleucine (I) at position 54 (N54I, p.Asn54Ile). 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 medium size and polar (N) to medium size and hydrophobic (I) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -3 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 CPVT4; increased RYR2 calcium-release channel activity; not changed calcium-dependent inactivation of L-type calcium channel; not changed protein abundance; not changed structure; not changed thermal stability both in the absence and presence of calcium; no effect on the calcium binding affinity; significantly increased binding of RYR2; increased ryanodine-sensitive calcium-release channel activity; decreased of KCNN2 calcium-activated potassium channel activity; not changed KCNN2 expression; not changed KCNN2 location at membrane. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 54 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 149 The length of the canonical sequence.
Location on the sequence: help GTVMRSLGQNPTEAELQDMI N EVDADGNGTIDFPEFLTMMA 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                         GTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTMMA

Mouse                         GTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTMMA

Rat                           GTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTMMA

Xenopus laevis                GTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTMMA
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 2 – 149 Calmodulin-1
Domain 44 – 79 EF-hand 2
Binding site 57 – 57
Binding site 59 – 59
Binding site 61 – 61
Binding site 63 – 63
Binding site 68 – 68
Modified residue 45 – 45 Phosphothreonine; by CaMK4
Helix 46 – 56



Literature citations
Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death.
Nyegaard M.; Overgaard M.T.; Sondergaard M.T.; Vranas M.; Behr E.R.; Hildebrandt L.L.; Lund J.; Hedley P.L.; Camm A.J.; Wettrell G.; Fosdal I.; Christiansen M.; Borglum A.D.;
Am. J. Hum. Genet. 91:703-712(2012)
Cited for: INVOLVEMENT IN CPVT4; VARIANTS CPVT4 ILE-54 AND SER-98; CHARACTERIZATION OF VARIANTS CPVT4 ILE-54 AND SER-98; Distinctive malfunctions of calmodulin mutations associated with heart RyR2-mediated arrhythmic disease.
Vassilakopoulou V.; Calver B.L.; Thanassoulas A.; Beck K.; Hu H.; Buntwal L.; Smith A.; Theodoridou M.; Kashir J.; Blayney L.; Livaniou E.; Nounesis G.; Lai F.A.; Nomikos M.;
Biochim. Biophys. Acta 1850:2168-2176(2015)
Cited for: VARIANTS CPVT4 ILE-54 AND SER-98; CHARACTERIZATION OF VARIANTS CPVT4 ILE-54 AND SER-98; VARIANTS LQT14 GLY-130 AND LEU-142; CHARACTERIZATION OF VARIANTS LQT14 GLY-130 AND LEU-142; INTERACTION WITH RYR2; Novel CPVT-Associated Calmodulin Mutation in CALM3 (CALM3-A103V) Activates Arrhythmogenic Ca Waves and Sparks.
Gomez-Hurtado N.; Boczek N.J.; Kryshtal D.O.; Johnson C.N.; Sun J.; Nitu F.R.; Cornea R.L.; Chazin W.J.; Calvert M.L.; Tester D.J.; Ackerman M.J.; Knollmann B.C.;
Circ. Arrhythm. Electrophysiol. 9:0-0(2016)
Cited for: VARIANTS CPVT4 ILE-54 AND SER-98; CHARACTERIZATION OF VARIANTS CPVT4 ILE-54; SER-98; INTERACTION WITH RYR2; Arrhythmogenic calmodulin mutations impede activation of small-conductance calcium-activated potassium current.
Yu C.C.; Ko J.S.; Ai T.; Tsai W.C.; Chen Z.; Rubart M.; Vatta M.; Everett T.H. IV; George A.L. Jr.; Chen P.S.;
Heart Rhythm 13:1716-1723(2016)
Cited for: VARIANTS CPVT4 ILE-54 AND SER-98; CHARACTERIZATION OF VARIANTS CPVT4 ILE-54 AND SER-98; VARIANTS LQT14 LEU-90 AND GLY-130; CHARACTERIZATION OF VARIANTS LQT14 LEU-90 AND GLY-130; FUNCTION;
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.