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UniProtKB/Swiss-Prot P0DP24: Variant p.Asp96Val

Calmodulin-2
Gene: CALM2
Variant information

Variant position:  96
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 Aspartate (D) to Valine (V) at position 96 (D96V, p.Asp96Val).
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 medium size and acidic (D) to medium size and hydrophobic (V)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -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:  In LQT15; reduction in calcium affinity; highly decreased calcium-dependent inactivation of L-type calcium channel; increased action potential duration; not changed protein abundance; not changed structure; increased thermal stability in absence of calcium; decreased thermal stability in presence of calcium; significantly increased RYR2 interaction; 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:  
Links to websites of interest for the variant.



Sequence information

Variant position:  96
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  149
The length of the canonical sequence.

Location on the sequence:   KMKDTDSEEEIREAFRVFDK  D GNGYISAAELRHVMTNLGEK
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                         KMKDTDSEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEK

Mouse                         KMKDTDSEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEK

Rat                           KMKDTDSEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEK

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.

TypePositionsDescription
Chain 2 – 149 Calmodulin-2
Domain 81 – 116 EF-hand 3
Calcium binding 94 – 105 3
Region 77 – 149 Necessary and sufficient for interaction with PCP4
Modified residue 82 – 82 Phosphoserine
Modified residue 95 – 95 N6-acetyllysine
Modified residue 100 – 100 Phosphotyrosine
Modified residue 102 – 102 Phosphoserine
Modified residue 111 – 111 Phosphothreonine
Modified residue 116 – 116 N6,N6,N6-trimethyllysine; alternate
Modified residue 116 – 116 N6-methyllysine; alternate


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 LQT15; VARIANT LQT15 VAL-96; CHARACTERIZATION OF VARIANT LQT15 VAL-96;

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: VARIANT LQT15 VAL-96; CHARACTERIZATION OF VARIANT LQT15 VAL-96; 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: VARIANT LQT15 VAL-96; CHARACTERIZATION OF VARIANT LQT15 VAL-96; 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: VARIANT LQT15 VAL-96; CHARACTERIZATION OF VARIANT LQT15 VAL-96; 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.