UniProtKB/Swiss-Prot P02545: Variant p.Arg377His

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 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 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

Involvement in disease:  Limb-girdle muscular dystrophy 1B (LGMD1B) [MIM:159001]: An autosomal dominant degenerative myopathy with age-related atrioventricular cardiac conduction disturbances, dilated cardiomyopathy, and the absence of early contractures. Characterized by slowly progressive skeletal muscle weakness of the hip and shoulder girdles. Muscle biopsy shows mild dystrophic changes. {ECO:0000269|PubMed:10814726, ECO:0000269|PubMed:11525883, ECO:0000269|PubMed:12032588, ECO:0000269|PubMed:12673789, ECO:0000269|PubMed:15744034, ECO:0000269|PubMed:17136397, ECO:0000269|PubMed:27234031}. 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 LGMD1B.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for 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.

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.







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.

Chain 1 – 661 Prelamin-A/C
Chain 1 – 646 Lamin-A/C
Domain 31 – 387 IF rod
Region 243 – 383 Coil 2
Modified residue 390 – 390 Phosphoserine
Modified residue 392 – 392 Phosphoserine
Modified residue 395 – 395 Phosphoserine
Cross 366 – 366 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Cross 378 – 378 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
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)

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.