UniProtKB/Swiss-Prot P02545: Variant p.Arg541His

Prelamin-A/C
Gene: LMNA
Chromosomal location: 1q21.2-q21.3
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Arginine (R) to Histidine (H) at position 541 (R541H, p.Arg541His).
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 (H)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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:  Emery-Dreifuss muscular dystrophy 2, autosomal dominant (EDMD2) [MIM:181350]: A form of Emery-Dreifuss muscular dystrophy, a degenerative myopathy characterized by weakness and atrophy of muscle without involvement of the nervous system, early contractures of the elbows, Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects. 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 EDMD2.
Any additional useful information about 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 432 – 545 LTD
Region 384 – 664 Tail
Modified residue 546 – 546 Phosphoserine
Alternative sequence 537 – 566 Missing. In isoform ADelta10.
Beta strand 537 – 543


Literature citations

Mutation analysis of the lamin A/C gene (LMNA) among patients with different cardiomuscular phenotypes.
Vytopil M.; Benedetti S.; Ricci E.; Galluzzi G.; Dello Russo A.; Merlini L.; Boriani G.; Gallina M.; Morandi L.; Politano L.; Moggio M.; Chiveri L.; Hausmanova-Petrusewicz I.; Ricotti R.; Vohanka S.; Toman J.; Toniolo D.;
J. Med. Genet. 40:E132-E132(2003)
Cited for: VARIANTS EDMD2 GLY-25; LYS-32 DEL; VAL-35; GLY-65; GLU-112 DEL; PRO-248; GLN-249; CYS-267; VAL-446; TRP-453; ARG-528 AND HIS-541; VARIANT CMD1A CYS-435;

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.