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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P0DP23: Variant p.Phe142Leu

Calmodulin-1
Gene: CALM1
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Variant information Variant position: help 142 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 Phenylalanine (F) to Leucine (L) at position 142 (F142L, p.Phe142Leu). 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 aromatic (F) to medium size and hydrophobic (L) 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 LQT14; reduction in calcium affinity; not changed protein abundance; not changed structure; significantly decreased thermal stability in presence of calcium; no effect on RYR2 interaction; significantly reduced ryanodine-sensitive calcium-release channel activity; impaired negative regulation of high voltage-gated calcium channel activity; impaired regulation of cardiac muscle cell action potential. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 142 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 VDEMIREADIDGDGQVNYEE F VQMMTAK 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                         VDEMIREADIDGDGQVNYEEFVQMMTAK

Mouse                         VDEMIREADIDGDGQVNYEEFVQMMTAK

Rat                           VDEMIREADIDGDGQVNYEEFVQMMTAK

Xenopus laevis                VDEMIREADIDGDGQVNYEEFVQMMTAK
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 117 – 149 EF-hand 4
Region 77 – 149 Necessary and sufficient for interaction with PCP4
Binding site 130 – 130
Binding site 132 – 132
Binding site 134 – 134
Binding site 136 – 136
Binding site 141 – 141
Modified residue 139 – 139 Phosphotyrosine
Helix 139 – 146



Literature citations
Calmodulin mutations associated with recurrent cardiac arrest in infants.
Crotti L.; Johnson C.N.; Graf E.; De Ferrari G.M.; Cuneo B.F.; Ovadia M.; Papagiannis J.; Feldkamp M.D.; Rathi S.G.; Kunic J.D.; Pedrazzini M.; Wieland T.; Lichtner P.; Beckmann B.M.; Clark T.; Shaffer C.; Benson D.W.; Kaab S.; Meitinger T.; Strom T.M.; Chazin W.J.; Schwartz P.J.; George A.L. Jr.;
Circulation 127:1009-1017(2013)
Cited for: INVOLVEMENT IN LQT14; VARIANTS LQT14 GLY-130 AND LEU-142; CHARACTERIZATION OF VARIANTS LQT14 GLY-130 AND LEU-142; 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; Spectrum and Prevalence of CALM1-, CALM2-, and CALM3-Encoded Calmodulin Variants in Long QT Syndrome and Functional Characterization of a Novel Long QT Syndrome-Associated Calmodulin Missense Variant, E141G.
Boczek N.J.; Gomez-Hurtado N.; Ye D.; Calvert M.L.; Tester D.J.; Kryshtal D.O.; Hwang H.S.; Johnson C.N.; Chazin W.J.; Loporcaro C.G.; Shah M.; Papez A.L.; Lau Y.R.; Kanter R.; Knollmann B.C.; Ackerman M.J.;
Circ. Cardiovasc. Genet. 9:136-146(2016)
Cited for: VARIANTS LQT14 GLY-141 AND LEU-142; CHARACTERIZATION OF VARIANT LQT14 GLY-141; FUNCTION; Elucidating arrhythmogenic mechanisms of long-QT syndrome CALM1-F142L mutation in patient-specific induced pluripotent stem cell-derived cardiomyocytes.
Rocchetti M.; Sala L.; Dreizehnter L.; Crotti L.; Sinnecker D.; Mura M.; Pane L.S.; Altomare C.; Torre E.; Mostacciuolo G.; Severi S.; Porta A.; De Ferrari G.M.; George A.L. Jr.; Schwartz P.J.; Gnecchi M.; Moretti A.; Zaza A.;
Cardiovasc. Res. 113:531-541(2017)
Cited for: CHARACTERIZATION OF VARIANT LQT14 LEU-142;
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.