UniProtKB/SwissProt variant VAR

Variant information

Variant position:

350

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 Arginine (R) to Proline (P) at position 350 (R350P, p.Arg350Pro).

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 basic (R) to medium size and hydrophobic (P)

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 Kaeser syndrome and MFM1; incapable of de novo formation of a desmin intermediate filaments network; exerts a dominant negative effect on the ordered lateral arrangement of desmin subunits; may produce structural changes; forms subsarcolemmal aggregates.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs57965306 [ dbSNP | Ensembl ]

Sequence information

Variant position:

350

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

Protein sequence length:

470

The length of the canonical sequence.

Location on the sequence:

SYTCEIDALKGTNDSLMRQM R ELEDRFASEASGYQDNIARL

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                         SYTCEIDALKGTNDSLMRQMRELEDRFASEASGYQDNIARL

Mouse                         SYTCEIDALKGTNDSLMRQMRELEDRFASEANGYQDNIARL

Rat                           SYTCEIDALKGTNDSLMRQMRELEDRFASEASGYQDNIARL

Pig                           SYTCEIDALKGTNDSLMRQMRELEDRFASEASGYQDNIARL

Bovine                        SYTCEIDALKGTNDSLMRQMRELEDRFASEASGYQDNIARL

Chicken                       SYTCEIDALKGTNDSLMRQMREMEERFAGEAGGYQDTIARL

Xenopus laevis                SYTCEIDALKGTNDSLMRQMRDLEEKFSGEAAGYQDTIGRL

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 – 470	Desmin
Domain	108 – 416	IF rod
Region	268 – 415	Interaction with NEB
Region	296 – 412	Coil 2B
Modified residue	358 – 358	Phosphoserine
Modified residue	361 – 361	Phosphoserine

Literature citations

Pathogenic effects of a novel heterozygous R350P desmin mutation on the assembly of desmin intermediate filaments in vivo and in vitro.
Baer H.; Fischer D.; Goudeau B.; Kley R.A.; Clemen C.S.; Vicart P.; Herrmann H.; Vorgerd M.; Schroeder R.;
Hum. Mol. Genet. 14:1251-1260(2005)
Cited for: VARIANT MFM1 PRO-350; CHARACTERIZATION OF VARIANT MFM1 PRO-350;

Scapuloperoneal syndrome type Kaeser and a wide phenotypic spectrum of adult-onset, dominant myopathies are associated with the desmin mutation R350P.
Walter M.C.; Reilich P.; Huebner A.; Fischer D.; Schroeder R.; Vorgerd M.; Kress W.; Born C.; Schoser B.G.; Krause K.H.; Klutzny U.; Bulst S.; Frey J.R.; Lochmueller H.;
Brain 130:1485-1496(2007)
Cited for: VARIANT KAESER SYNDROME PRO-350;

The toxic effect of R350P mutant desmin in striated muscle of man and mouse.
Clemen C.S.; Stoeckigt F.; Strucksberg K.H.; Chevessier F.; Winter L.; Schuetz J.; Bauer R.; Thorweihe J.M.; Wenzel D.; Schloetzer-Schrehardt U.; Rasche V.; Krsmanovic P.; Katus H.A.; Rottbauer W.; Just S.; Mueller O.J.; Friedrich O.; Meyer R.; Herrmann H.; Schrickel J.W.; Schroeder R.;
Acta Neuropathol. 129:297-315(2015)
Cited for: CHARACTERIZATION OF VARIANT KAESER SYNDROME PRO-350; CHARACTERIZATION OF VARIANT MFM1 PRO-350; FUNCTION; SUBCELLULAR LOCATION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P17661: Variant p.Arg350Pro