UniProtKB/SwissProt variant VAR

Variant information

Variant position:

90

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 Phenylalanine (F) to Leucine (L) at position 90 (F90L, p.Phe90Leu).

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 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:

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:

In LQT14; significantly decreased of KCNN2 calcium-activated potassium channel activity; not changed KCNN2 expression; not changed KCNN2 location at membrane; decreased thermal stability in presence of calcium ions; decreased interaction with RYR2.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs730882253 [ dbSNP | Ensembl ]

Sequence information

Variant position:

90

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:

LTMMARKMKDTDSEEEIREA F RVFDKDGNGYISAAELRHVM

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                         LTMMARKMKDTDSEEEIREAFRVFDKDGNGYISAAELRHVM

Mouse                         LTMMARKMKDTDSEEEIREAFRVFDKDGNGYISAAELRHVM

Rat                           LTMMARKMKDTDSEEEIREAFRVFDKDGNGYISAAELRHVM

Xenopus laevis                LTMMARKMKDTDSEEEIREAFRVFDKDGNGYISAAELRHVM

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-1
Domain	81 – 116	EF-hand 3
Region	77 – 149	Necessary and sufficient for interaction with PCP4
Metal binding	94 – 94	Calcium 3
Metal binding	96 – 96	Calcium 3
Metal binding	98 – 98	Calcium 3
Metal binding	100 – 100	Calcium 3
Metal binding	105 – 105	Calcium 3
Modified residue	82 – 82	Phosphoserine
Modified residue	95 – 95	N6-acetyllysine
Modified residue	100 – 100	Phosphotyrosine
Modified residue	102 – 102	Phosphoserine
Helix	66 – 93

Literature citations

Altered RyR2 regulation by the calmodulin F90L mutation associated with idiopathic ventricular fibrillation and early sudden cardiac death.
Nomikos M.; Thanassoulas A.; Beck K.; Vassilakopoulou V.; Hu H.; Calver B.L.; Theodoridou M.; Kashir J.; Blayney L.; Livaniou E.; Rizkallah P.; Nounesis G.; Lai F.A.;
FEBS Lett. 588:2898-2902(2014)
Cited for: CHARACTERIZATION OF VARIANT LQT14 LEU-90;

A mutation in CALM1 encoding calmodulin in familial idiopathic ventricular fibrillation in childhood and adolescence.
Marsman R.F.; Barc J.; Beekman L.; Alders M.; Dooijes D.; van den Wijngaard A.; Ratbi I.; Sefiani A.; Bhuiyan Z.A.; Wilde A.A.; Bezzina C.R.;
J. Am. Coll. Cardiol. 63:259-266(2014)
Cited for: INVOLVEMENT IN LQT14; VARIANT LQT14 LEU-90;

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;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P0DP23: Variant p.Phe90Leu