UniProtKB/Swiss-Prot P02545: Variant p.Arg399Cys

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

Variant position:  399
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 Cysteine (C) at position 399 (R399C, p.Arg399Cys).
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. 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.

Involvement in disease:  Lipodystrophy, familial partial, 2 (FPLD2) [MIM:151660]: A disorder characterized by the loss of subcutaneous adipose tissue in the lower parts of the body (limbs, buttocks, trunk). It is accompanied by an accumulation of adipose tissue in the face and neck causing a double chin, fat neck, or cushingoid appearance. Adipose tissue may also accumulate in the axillae, back, labia majora, and intraabdominal region. Affected patients are insulin-resistant and may develop glucose intolerance and diabetes mellitus after age 20 years, hypertriglyceridemia, and low levels of high density lipoprotein cholesterol. 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 FPLD2 and CMD1A; no effect on nuclear morphology and lamin A localization.
Any additional useful information about the variant.



Sequence information

Variant position:  399
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:   LLEGEEERLRLSPSPTSQRS  R GRASSHSSQTQGGGSVTKKR
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                         LLEGEEERLRLSPSPTSQRSRGRASSHSSQTQGGGSVTKKR

Mouse                         LLEGEEERLRLSPSPTSQRSRGRASSHSSQSQGGGSVTKKR

Rat                           LLEGEEERLRLSPSPTSQRSRGRASSHSSQSQGGGSVTKKR

Pig                           LLEGEEERLRLSPSPTSQRSRGRASSHSSQTQSGGSVTKKR

Chicken                       LLEGEEERLRLSPSPSSQ----RGARSSGLQHSGAGSAKKR

Xenopus laevis                LLEGEEERLRLSPSPNTQKRSARTIASHSGAHISSSASKRR

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 384 – 664 Tail
Modified residue 390 – 390 Phosphoserine
Modified residue 392 – 392 Phosphoserine
Modified residue 395 – 395 Phosphoserine
Modified residue 404 – 404 Phosphoserine
Modified residue 407 – 407 Phosphoserine
Modified residue 414 – 414 Phosphoserine


Literature citations

Morphological analysis of 13 LMNA variants identified in a cohort of 324 unrelated patients with idiopathic or familial dilated cardiomyopathy.
Cowan J.; Li D.; Gonzalez-Quintana J.; Morales A.; Hershberger R.E.;
Circ. Cardiovasc. Genet. 3:6-14(2010)
Cited for: SUBCELLULAR LOCATION; VARIANTS CMD1A LEU-89; PRO-101; PRO-166; GLN-190; LYS-203; SER-210; PRO-215; THR-318; HIS-388; CYS-399 AND HIS-471;

Novel LMNA mutations seen in patients with familial partial lipodystrophy subtype 2 (FPLD2; MIM 151660).
Lanktree M.; Cao H.; Rabkin S.W.; Hanna A.; Hegele R.A.;
Clin. Genet. 71:183-186(2007)
Cited for: VARIANTS FPLD2 ASN-230; CYS-399 AND LEU-573;

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.