UniProtKB/SwissProt variant VAR

Variant information

Variant position:

451

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 Isoleucine (I) to Methionine (M) at position 451 (I451M, p.Ile451Met).

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:

Similar physico-chemical property. Both residues are medium size and hydrophobic.

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 CMD1I and MFM1; reveals a severe disturbance of filament-formation competence and filament-filament interactions; reduced interaction with CRYAB.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121913002 [ dbSNP | Ensembl ]

Sequence information

Variant position:

451

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:

TSPEQRGSEVHTKKTVMIKT I ETRDGEVVSEATQQQHEVL

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                         TSPEQRGSEVHTKKTVMIKTIETRDGEVVSEATQQQHEVL

Mouse                         TSPEQRGSEVHTKKTVMIKTIETRDGEVVSEATQQQHEVL

Rat                           TSPEQRGSEVHTKKTVMIKTIETRDGEVVSEATQQQHEVL

Pig                           TSPEQRGSEVHTKKTVMIKTIETRDGEVVSEATQQQHEVL

Bovine                        TSPEQRGSEVHTKKTVMIKTIETRDGEVVSEATQQQHEVL

Chicken                       TSPDQRGSEVHTKKTVMIKTIETRDGEVVSEATQQQHEVL

Xenopus laevis                TSPEQRASEVHTKKTVMIKTIETRDGEVLSEASQQHQEIL

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
Region	413 – 470	Tail
Region	438 – 453	Interaction with CRYAB

Literature citations

Desmin mutation responsible for idiopathic dilated cardiomyopathy.
Li D.; Tapscoft T.; Gonzalez O.; Burch P.E.; Quinones M.A.; Zoghbi W.A.; Hill R.; Bachinski L.L.; Mann D.L.; Roberts R.;
Circulation 100:461-464(1999)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; VARIANT CMD1I MET-451; INVOLVEMENT IN CMD1I;

Desmin myopathy, a skeletal myopathy with cardiomyopathy caused by mutations in the desmin gene.
Dalakas M.C.; Park K.-Y.; Semino-Mora C.; Lee H.S.; Sivakumar K.; Goldfarb L.G.;
N. Engl. J. Med. 342:770-780(2000)
Cited for: VARIANTS MFM1 PRO-337; ASP-342; PRO-360; ILE-393; TRP-406 AND MET-451; CHARACTERIZATION OF VARIANTS MFM1 PRO-337; ASP-342; PRO-360; ILE-393; TRP-406 AND MET-451;

Conspicuous involvement of desmin tail mutations in diverse cardiac and skeletal myopathies.
Baer H.; Goudeau B.; Waelde S.; Casteras-Simon M.; Muecke N.; Shatunov A.; Goldberg Y.P.; Clarke C.; Holton J.L.; Eymard B.; Katus H.A.; Fardeau M.; Goldfarb L.; Vicart P.; Herrmann H.;
Hum. Mutat. 28:374-386(2007)
Cited for: VARIANTS MFM1 ILE-442; TRP-454 AND ILE-460; CHARACTERIZATION OF VARIANTS MFM1 ILE-442; MET-451; TRP-454 AND ILE-460;

alphaB-crystallin is a sensor for assembly intermediates and for the subunit topology of desmin intermediate filaments.
Sharma S.; Conover G.M.; Elliott J.L.; Der Perng M.; Herrmann H.; Quinlan R.A.;
Cell Stress Chaperones 22:613-626(2017)
Cited for: CHARACTERIZATION OF VARIANTS MFM1 MET-451 AND TRP-454; INTERACTION WITH CRYAB;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P17661: Variant p.Ile451Met