UniProtKB/SwissProt variant VAR

Variant information

Variant position:

103

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

Type of variant:

Disease [Disclaimer]

The variants are classified into three categories: Disease, Polymorphism and Unclassified.

Disease: Variants implicated in disease according to literature reports.
Polymorphism: Variants not reported to be implicated in disease.
Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:

From Alanine (A) to Valine (V) at position 103 (A103V, p.Ala103Val).

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 small size and hydrophobic (A) to medium size and hydrophobic (V)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

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:

Probable disease-associated variant found in a patient with CPVT; decreased calcium-binding affinity; not changed binding to RYR2; increased RYR2 calcium-release channel activity; decreased calcium-dependent inactivation of L-type calcium channel; not changed action potential duration.

Any additional useful information about the variant.

Sequence information

Variant position:

103

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:

EEEIREAFRVFDKDGNGYIS A AELRHVMTNLGEKLTDEEVD

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                         EEEIREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVD

Mouse                         EEEIREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVD

Rat                           EEEIREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVD

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	2 – 149	Calmodulin-3
Domain	81 – 116	EF-hand 3
Calcium binding	94 – 105	3
Region	77 – 149	Necessary and sufficient for interaction with PCP4
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

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 CPVT VAL-103; CHARACTERIZATION OF VARIANT CPVT VAL-103; INTERACTION WITH RYR2;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P0DP25: Variant p.Ala103Val