UniProtKB/SwissProt variant VAR

Variant information

Variant position:

627

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 Proline (P) to Histidine (H) at position 627 (P627H, p.Pro627His).

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 hydrophobic (P) to medium size and polar (H)

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

Involvement in disease:

Myopathy, centronuclear, 1 (CNM1) [MIM:160150]: A congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers. {ECO:0000269|PubMed:16227997, ECO:0000269|PubMed:17825552, ECO:0000269|PubMed:17932957, ECO:0000269|PubMed:19122038, ECO:0000269|PubMed:19623537, ECO:0000269|PubMed:19932619, ECO:0000269|PubMed:19932620, ECO:0000269|PubMed:20227276, ECO:0000269|PubMed:22396310}. Note=The disease is caused by mutations affecting the gene represented in this entry.

The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:

In CNM1.

Any additional useful information about the variant.

Sequence information

Variant position:

627

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

Protein sequence length:

870

The length of the canonical sequence.

Location on the sequence:

CDSQEDVDSWKASFLRAGVY P EKDQAENEDGAQENTFSMDP

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                         CDSQEDVDSWKASFLRAGVYPEKDQAENEDGAQENTFSMDP

Mouse                         CDSQEDVDSWKASFLRAGVYPEKDQAENEDGAQENTFSMDP

Rat                           CDSQEDVDSWKASFLRAGVYPEKDQAENEDGAQENTFSMDP

Bovine                        CDSQEDVDSWKASFLRAGVYPEKDQAENEDGAQENTFSMDP

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 – 870	Dynamin-2

Literature citations

Expanding the clinical, pathological and MRI phenotype of DNM2-related centronuclear myopathy.
Susman R.D.; Quijano-Roy S.; Yang N.; Webster R.; Clarke N.F.; Dowling J.; Kennerson M.; Nicholson G.; Biancalana V.; Ilkovski B.; Flanigan K.M.; Arbuckle S.; Malladi C.; Robinson P.; Vucic S.; Mayer M.; Romero N.B.; Urtizberea J.A.; Garcia-Bragado F.; Guicheney P.; Bitoun M.; Carlier R.Y.; North K.N.;
Neuromuscul. Disord. 20:229-237(2010)
Cited for: VARIANTS CNM1 LYS-368; TRP-465; HIS-522; THR-618; LEU-619 AND HIS-627;

UniProtKB/Swiss-Prot P50570: Variant p.Pro627His