UniProtKB/Swiss-Prot Q9BR39: Variant p.Glu169Lys

Junctophilin-2
Gene: JPH2
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Variant information Variant position:

169 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US 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 Glutamate (E) to Lysine (K) at position 169 (E169K, p.Glu169Lys). 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 (E) to large size and basic (K) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

1 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:

Found in a patient with atrial fibrillation; likely pathogenic. Any additional useful information about the variant.

Sequence information Variant position:

169 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

696 The length of the canonical sequence.
Location on the sequence:

YGMAVVVRSPLRTSLSSLRS E HSNGTVAPDSPASPASDGPA 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                         YGMAVVVRSPLRTSLSSLRSEHSNGTVAPDSPASPASDGPA

Mouse                         YGMAVVVRSPLRTSLSSLRSEHSNGTVAPD---SPAADGPM

Rat                           YGMAVVVRSPLRTSLSSLRSEHSNGTVAPD---SPAADGPT

Rabbit                        YGMAVVVRSPLRTSLSSLRSEHSNGTVAPDSPASPAADGPA

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	1 – 696	Junctophilin-2
Chain	1 – 572	Junctophilin-2 N-terminal fragment
Topological domain	1 – 674	Cytoplasmic
Region	164 – 193	Disordered
Compositional bias	164 – 179	Polar residues
Modified residue	162 – 162	Phosphoserine
Modified residue	165 – 165	Phosphoserine
Alternative sequence	130 – 696	Missing. In isoform 2.

Literature citations
Mutation E169K in junctophilin-2 causes atrial fibrillation due to impaired RyR2 stabilization.
Beavers D.L.; Wang W.; Ather S.; Voigt N.; Garbino A.; Dixit S.S.; Landstrom A.P.; Li N.; Wang Q.; Olivotto I.; Dobrev D.; Ackerman M.J.; Wehrens X.H.T.;
J. Am. Coll. Cardiol. 62:2010-2019(2013)
Cited for: VARIANT LYS-169;

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.