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UniProtKB/Swiss-Prot P02545: Variant p.Arg541Cys

Prelamin-A/C
Gene: LMNA
Variant information

Variant position:  541
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 Cysteine (C) at position 541 (R541C, p.Arg541Cys).
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 polar (C)
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; grossly abnormal nuclear shape with the nuclear envelope producing prominent lobules in about 10% of cultured skin fibroblasts from heterozygous patients.
Any additional useful information about the variant.

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



Sequence information

Variant position:  541
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:   GCGNSLRTALINSTGEEVAM  R KLVRSVTVVEDDEDEDGDDL
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                         GCGNSLRTALINSTGEEVAMRKLVRSVTVVEDDEDE--DGDDL

Mouse                         GCGSSLRTALINSTGEEVAMRKLVRSLTMVEDNEDDDEDGE

Rat                           GCGTSLRTALINATGEEVAMRKLVRSLTMVEDNDDEEEDGD

Pig                           GCGNSLRTALINSTGEEVAMRKLVRSVTMIEDDEDE--DGD

Chicken                       GSGDSLRTALINSNGEEVAMRKLVRTVIINDDDEDEEDDEV

Xenopus laevis                GTGDSIRTALLTSSNEEVAMRKLVRTVVINDEDDEDNDDME

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 428 – 545 LTD
Region 384 – 664 Tail
Modified residue 533 – 533 Phosphoserine
Modified residue 546 – 546 Phosphoserine
Modified residue 548 – 548 Phosphothreonine
Alternative sequence 537 – 566 Missing. In isoform ADelta10.
Beta strand 537 – 543


Literature citations

Apical left ventricular aneurysm without atrio-ventricular block due to a lamin A/C gene mutation.
Forissier J.-F.; Bonne G.; Bouchier C.; Duboscq-Bidot L.; Richard P.; Wisnewski C.; Briault S.; Moraine C.; Dubourg O.; Schwartz K.; Komajda M.;
Eur. J. Heart Fail. 5:821-825(2003)
Cited for: VARIANT CMD1A CYS-541;

Nuclear envelope alterations in fibroblasts from patients with muscular dystrophy, cardiomyopathy, and partial lipodystrophy carrying lamin A/C gene mutations.
Muchir A.; Medioni J.; Laluc M.; Massart C.; Arimura T.; van der Kooi A.J.; Desguerre I.; Mayer M.; Ferrer X.; Briault S.; Hirano M.; Worman H.J.; Mallet A.; Wehnert M.; Schwartz K.; Bonne G.;
Muscle Nerve 30:444-450(2004)
Cited for: SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS EDMD2 LYS-32 DEL; SER-63; GLN-249; LYS-358; CYS-401; TRP-453 AND PRO-527; CHARACTERIZATION OF VARIANTS EDMD2 LYS-208 DEL AND HIS-377; CHARACTERIZATION OF VARIANT FPLD2 LEU-482; CHARACTERIZATION OF VARIANT CMD1A CYS-541;

Dilated cardiomyopathy with profound segmental wall motion abnormalities and ventricular arrhythmia caused by the R541C mutation in the LMNA gene.
Saj M.; Jankowska A.; Lewandowski M.; Szwed H.; Szperl M.; Ploski R.; Bilinska Z.T.;
Int. J. Cardiol. 144:E51-E53(2010)
Cited for: VARIANT CMD1A CYS-541;

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.