UniProtKB/Swiss-Prot P02545: Variant p.Arg377His

Prelamin-A/C
Gene: LMNA
Chromosomal location: 1q21.2-q21.3
Variant information

Variant position:  377
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 377 (R377H, p.Arg377His).
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

Variant description:  In LGMD1B.
Any additional useful information about the variant.



Sequence information

Variant position:  377
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:   DEYQELLDIKLALDMEIHAY  R KLLEGEEERLRLSPSPTSQR
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                         DEYQELLDIKLALDMEIHAYRKLLEGEEERLRLSPSPTSQR

Mouse                         DEYQELLDIKLALDMEIHAYRKLLEGEEERLRLSPSPTSQR

Rat                           DEYQELLDIKLALDMEIHAYRKLLEGEEERLRLSPSPTSQR

Pig                           DEYQELLDIKLALDMEIHAYRKLLEGEEERLRLSPSPTSQR

Chicken                       DEYQELLDIKLALDMEINAYRKLLEGEEERLRLSPSPSSQ-

Xenopus laevis                DEYQELLDIKLALDMEINAYRKLLEGEEERLRLSPSPNTQK

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
Region 34 – 383 Rod
Region 243 – 383 Coil 2
Modified residue 390 – 390 Phosphoserine
Modified residue 392 – 392 Phosphoserine
Modified residue 395 – 395 Phosphoserine
Helix 316 – 384


Literature citations

Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbances (LGMD1B).
Muchir A.; Bonne G.; van der Kooi A.J.; van Meegen M.; Baas F.; Bolhuis P.A.; de Visser M.; Schwartz K.;
Hum. Mol. Genet. 9:1453-1459(2000)
Cited for: VARIANTS LGMD1B LYS-208 DEL AND HIS-377;

Functional consequences of an LMNA mutation associated with a new cardiac and non-cardiac phenotype.
Charniot J.-C.; Pascal C.; Bouchier C.; Sebillon P.; Salama J.; Duboscq-Bidot L.; Peuchmaurd M.; Desnos M.; Artigou J.-Y.; Komajda M.;
Hum. Mutat. 21:473-481(2003)
Cited for: VARIANT LGMD1B HIS-377;

Natural history of dilated cardiomyopathy due to lamin A/C gene mutations.
Taylor M.R.G.; Fain P.R.; Sinagra G.; Robinson M.L.; Robertson A.D.; Carniel E.; Di Lenarda A.; Bohlmeyer T.J.; Ferguson D.A.; Brodsky G.L.; Boucek M.M.; Lascor J.; Moss A.C.; Li W.-L.P.; Stetler G.L.; Muntoni F.; Bristow M.R.; Mestroni L.;
J. Am. Coll. Cardiol. 41:771-780(2003)
Cited for: VARIANTS CMD1A LEU-89; HIS-377 AND LEU-573;

Lamin A N-terminal phosphorylation is associated with myoblast activation: impairment in Emery-Dreifuss muscular dystrophy.
Cenni V.; Sabatelli P.; Mattioli E.; Marmiroli S.; Capanni C.; Ognibene A.; Squarzoni S.; Maraldi N.M.; Bonne G.; Columbaro M.; Merlini L.; Lattanzi G.;
J. Med. Genet. 42:214-220(2005)
Cited for: VARIANT LGMD1B HIS-377; VARIANTS EDMD2 ASN-63; PRO-140; GLN-190; GLN-249 AND PRO-527;

Mutations of the LMNA gene can mimic autosomal dominant proximal spinal muscular atrophy.
Rudnik-Schoeneborn S.; Botzenhart E.; Eggermann T.; Senderek J.; Schoser B.G.H.; Schroeder R.; Wehnert M.; Wirth B.; Zerres K.;
Neurogenetics 8:137-142(2007)
Cited for: VARIANT LGMD1B HIS-377;

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.