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UniProtKB/Swiss-Prot P02545: Variant p.Arg190Trp

Prelamin-A/C
Gene: LMNA
Variant information

Variant position:  190
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 Arginine (R) to Tryptophan (W) at position 190 (R190W, p.Arg190Trp).
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 large size and aromatic (W)
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 1A (CMD1A) [MIM:115200]: 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:10580070, ECO:0000269|PubMed:11561226, ECO:0000269|PubMed:11792809, ECO:0000269|PubMed:11897440, ECO:0000269|PubMed:12486434, ECO:0000269|PubMed:12628721, ECO:0000269|PubMed:12920062, ECO:0000269|PubMed:14675861, ECO:0000269|PubMed:14684700, ECO:0000269|PubMed:15140538, ECO:0000269|PubMed:15219508, ECO:0000269|PubMed:15372542, ECO:0000269|PubMed:16061563, ECO:0000269|PubMed:18606848, ECO:0000269|PubMed:19167105, ECO:0000269|PubMed:20160190, ECO:0000269|PubMed:21846512}. 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 CMD1A.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  190
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  664
The length of the canonical sequence.

Location on the sequence:   AKLEAALGEAKKQLQDEMLR  R VDAENRLQTMKEELDFQKNI
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                         AKLEAALGEAKKQLQDEMLRRVDAENRLQTMKEELDFQKNI

Mouse                         AKLEAALGEAKKQLQDEMLRRVDAENRLQTLKEELDFQKNI

Rat                           AKLEAALGEAKKQLQDEMLRRVDAENRLQTLKEELDFQKNI

Pig                           AKLEAALGEAKKQLQDEMLRRVDAENRLQTLKEELDFQKNI

Chicken                       AKLEGALSEAKKQLQDEMLRRVDAENRLQTLKEELEFQKNI

Xenopus laevis                AKLEASLADTKKQLQDEMLRRVDTENRNQTLKEELEFQKSI

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.

TypePositionsDescription
Chain 1 – 661 Prelamin-A/C
Chain 1 – 646 Lamin-A/C
Domain 31 – 387 IF rod
Region 81 – 218 Coil 1B
Modified residue 171 – 171 N6-acetyllysine; alternate
Modified residue 171 – 171 N6-succinyllysine; alternate
Modified residue 201 – 201 N6-acetyllysine; alternate
Cross 171 – 171 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate
Cross 201 – 201 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate
Cross 201 – 201 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate
Cross 208 – 208 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Mutagenesis 201 – 201 K -> L. Decreased sumoylation; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; associated with increased cell death.


Literature citations

In vivo and in vitro examination of the functional significances of novel lamin gene mutations in heart failure patients.
Sylvius N.; Bilinska Z.T.; Veinot J.P.; Fidzianska A.; Bolongo P.M.; Poon S.; McKeown P.; Davies R.A.; Chan K.-L.; Tang A.S.L.; Dyack S.; Grzybowski J.; Ruzyllo W.; McBride H.; Tesson F.;
J. Med. Genet. 42:639-647(2005)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A); SUBCELLULAR LOCATION (ISOFORM C); VARIANTS CMD1A TRP-190; GLY-192 AND SER-541; CHARACTERIZATION OF VARIANTS CMD1A GLY-192 AND SER-541;

Autosomal dominant dilated cardiomyopathy with atrioventricular block: a lamin A/C defect-related disease.
Arbustini E.; Pilotto A.; Repetto A.; Grasso M.; Negri A.; Diegoli M.; Campana C.; Scelsi L.; Baldini E.; Gavazzi A.; Tavazzi L.;
J. Am. Coll. Cardiol. 39:981-990(2002)
Cited for: VARIANTS CMD1A GLU-97; TRP-190 AND LYS-317;

Familial dilated cardiomyopathy and isolated left ventricular noncompaction associated with lamin A/C gene mutations.
Hermida-Prieto M.; Monserrat L.; Castro-Beiras A.; Laredo R.; Soler R.; Peteiro J.; Rodriguez E.; Bouzas B.; Alvarez N.; Muniz J.; Crespo-Leiro M.;
Am. J. Cardiol. 94:50-54(2004)
Cited for: VARIANTS CMD1A TRP-190 AND LEU-349;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.