UniProtKB/SwissProt variant VAR

Variant information

Variant position:

136

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 Leucine (L) to Proline (P) at position 136 (L136P, p.Leu136Pro).

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:

-3

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:

Cardiomyopathy, dilated 1I (CMD1I) [MIM:604765]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:10430757, ECO:0000269|PubMed:24200904, ECO:0000269|PubMed:26724190}. 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 CMD1I; results in impaired filaments formation, does not localize at intercalated disks.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs397516695 [ dbSNP | Ensembl ]

Sequence information

Variant position:

136

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:

NDRFANYIEKVRFLEQQNAA L AAEVNRLKGREPTRVAELYE

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                         NDRFANYIEKVRFLEQQNAALAAEVNRLKGREPTRVAELYE

                              NDRFANYIEKVRFLEQQNAALAAEVNRLKGREPTRVAEIYE

Mouse                         NDRFANYIEKVRFLEQQNAALAAEVNRLKGREPTRVAELYE

Rat                           NDRFANYFEKVRFLEQQNAALAAEVNRLKGREPTRVAELYE

Pig                           NDRFANYIEKVRFLEQQNAALAAEVNRLKGREPTRVAEIYE

Bovine                        NDRFANYIEKVRFLEQQNAALAAEVNRLKGREPTRVAEIYE

Chicken                       NDRFANYIEKVRFLEQQNALMVAEVNRLRGKQPTRVAEMYE

Xenopus laevis                NDRFANYIEKVRYLEQQNQILVAEVNRLKGKEPTRVNELYE

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 – 470	Desmin
Domain	108 – 416	IF rod
Region	109 – 141	Coil 1A
Mutagenesis	120 – 120	A -> ER. Results in impaired filaments formation.
Mutagenesis	120 – 120	A -> KLV. Does not result in impaired filaments formation.

Literature citations

Functional characterization of the novel DES mutation p.L136P associated with dilated cardiomyopathy reveals a dominant filament assembly defect.
Brodehl A.; Dieding M.; Biere N.; Unger A.; Klauke B.; Walhorn V.; Gummert J.; Schulz U.; Linke W.A.; Gerull B.; Vorgert M.; Anselmetti D.; Milting H.;
J. Mol. Cell. Cardiol. 91:207-214(2016)
Cited for: VARIANT CMD1I PRO-136; CHARACTERIZATION OF VARIANT CMD1I PRO-136; FUNCTION; SUBCELLULAR LOCATION;

UniProtKB/Swiss-Prot P17661: Variant p.Leu136Pro