UniProtKB/SwissProt variant VAR

Variant information

Variant position:

3340

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 Cysteine (C) to Tyrosine (Y) at position 3340 (C3340Y, p.Cys3340Tyr).

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 polar (C) to large size and aromatic (Y)

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

BLOSUM score:

-2

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 DMD; results in highly reduced protein levels and expression at the sarcolemma.

Any additional useful information about the variant.

Sequence information

Variant position:

3340

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

Protein sequence length:

3685

The length of the canonical sequence.

Location on the sequence:

PIIGFRYRSLKHFNYDICQS C FFSGRVAKGHKMHYPMVEYC

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                         PIIGFRYRSLKHFNYDICQSCFFSGRVAKGHKMHYPMVEYC

                              PIIGFRYRSLKHFNYDICQSCFFSGRVAKGHKMHYPMVEYC

Mouse                         PIIGFRYRSLKHFNYDICQSCFFSGRVAKGHKMHYPMVEYC

Rat                           PIIGFRYRSLKHFNYDICQSCFFSGRVAKGHKMHYPMVEYC

Pig                           PIIGFRYRSLKHFNYDICQSCFFSGRVAKGHKMHYPMVEYC

Chicken                       PIIGFRYRSLKHFNYDICQSCFFSGRVAKGHKMHYPMVEYC

Caenorhabditis elegans        PIIGIRYRCLTCFNCDLCQNCFFSQRTAKSHRTNHPMQEYC

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 – 3685	Dystrophin
Zinc finger	3308 – 3364	ZZ-type; degenerate
Region	3058 – 3408	Interaction with SYNM
Metal binding	3337 – 3337	Zinc
Metal binding	3340 – 3340	Zinc

Literature citations

A cysteine 3340 substitution in the dystroglycan-binding domain of dystrophin associated with Duchenne muscular dystrophy, mental retardation and absence of the ERG b-wave.
Lenk U.; Oexle K.; Voit T.; Ancker U.; Hellner K.A.; Speer A.; Hubner C.;
Hum. Mol. Genet. 5:973-975(1996)
Cited for: VARIANT DMD TYR-3340;

The ZZ domain of dystrophin in DMD: making sense of missense mutations.
Vulin A.; Wein N.; Strandjord D.M.; Johnson E.K.; Findlay A.R.; Maiti B.; Howard M.T.; Kaminoh Y.J.; Taylor L.E.; Simmons T.R.; Ray W.C.; Montanaro F.; Ervasti J.M.; Flanigan K.M.;
Hum. Mutat. 35:257-264(2014)
Cited for: CHARACTERIZATION OF VARIANTS DMD PHE-3313; HIS-3335 AND TYR-3340;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P11532: Variant p.Cys3340Tyr