UniProtKB/SwissProt variant VAR

Variant information

Variant position:

357

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 Alanine (A) to Proline (P) at position 357 (A357P, p.Ala357Pro).

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 small size and hydrophobic (A) to medium size and hydrophobic (P)

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:

In MFM1; unable to polymerize and form an intracellular filamentous network; abolishes binding to MTM1.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs58898021 [ dbSNP | Ensembl ]

Sequence information

Variant position:

357

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:

ALKGTNDSLMRQMRELEDRF A SEASGYQDNIARLEEEIRHL

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                         ALKGTNDSLMRQMRELEDRFASEASGYQDNIARLEEEIRHL

Mouse                         ALKGTNDSLMRQMRELEDRFASEANGYQDNIARLEEEIRHL

Rat                           ALKGTNDSLMRQMRELEDRFASEASGYQDNIARLEEEIRHL

Pig                           ALKGTNDSLMRQMRELEDRFASEASGYQDNIARLEEEIRHL

Bovine                        ALKGTNDSLMRQMRELEDRFASEASGYQDNIARLEEEIRHL

Chicken                       ALKGTNDSLMRQMREMEERFAGEAGGYQDTIARLEEEIRHL

Xenopus laevis                ALKGTNDSLMRQMRDLEEKFSGEAAGYQDTIGRLEEEIRNM

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

Small deletions disturb desmin architecture leading to breakdown of muscle cells and development of skeletal or cardioskeletal myopathy.
Kaminska A.; Strelkov S.V.; Goudeau B.; Olive M.; Dagvadorj A.; Fidzianska A.; Simon-Casteras M.; Shatunov A.; Dalakas M.C.; Ferrer I.; Kwiecinski H.; Vicart P.; Goldfarb L.G.;
Hum. Genet. 114:306-313(2004)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS MFM1 ASP-342; PRO-357; 359-GLU--SER-361 DEL; ASN-366 DEL AND PRO-370; VARIANT VAL-213;

Myotubularin controls desmin intermediate filament architecture and mitochondrial dynamics in human and mouse skeletal muscle.
Hnia K.; Tronchere H.; Tomczak K.K.; Amoasii L.; Schultz P.; Beggs A.H.; Payrastre B.; Mandel J.L.; Laporte J.;
J. Clin. Invest. 121:70-85(2011)
Cited for: INTERACTION WITH MTM1; CHARACTERIZATION OF VARIANTS ASP-342; PRO-357; PRO-360 AND PRO-370; SUBUNIT;

Respiratory insufficiency in desminopathy patients caused by introduction of proline residues in desmin C-terminal alpha-helical segment.
Dagvadorj A.; Goudeau B.; Hilton-Jones D.; Blancato J.K.; Shatunov A.; Simon-Casteras M.; Squier W.; Nagle J.W.; Goldfarb L.G.; Vicart P.;
Muscle Nerve 27:669-675(2003)
Cited for: VARIANTS MFM1 PRO-357 AND PRO-370; CHARACTERIZATION OF VARIANTS MFM1 PRO-357 AND PRO-370;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P17661: Variant p.Ala357Pro