UniProtKB/Swiss-Prot P02545: Variant p.Arg249Gln

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

Variant position:  249
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 Glutamine (Q) at position 249 (R249Q, p.Arg249Gln).
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 (Q)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  1
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 EDMD2.
Any additional useful information about the variant.



Sequence information

Variant position:  249
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:   IDNGKQREFESRLADALQEL  R AQHEDQVEQYKKELEKTYSA
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                         IDNGKQREFESRLADALQELRAQHEDQVEQYKKELEKTYSA

Mouse                         IDNGKQREFESRLADALQELRAQHEDQVEQYKKELEKTYSA

Rat                           IDNGKQREFESRLADALQELRAQHEDQVEQYKKELEKTYSA

Pig                           IDNGKQREFESRLADALQDLRAQHEDQVEQYKKELEKTYSA

Chicken                       IDNGRQQEFESKLAEALQDLRRQHEDQIRHYRDELEKTYGA

Xenopus laevis                VDNGRQREFESKLADALHELRAQHEGQIGLYKEELGKTYNA

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
Site 266 – 266 Heptad change of phase
Modified residue 260 – 260 N6-acetyllysine


Literature citations

Different mutations in the LMNA gene cause autosomal dominant and autosomal recessive Emery-Dreifuss muscular dystrophy.
Raffaele di Barletta M.; Ricci E.; Galluzzi G.; Tonali P.; Mora M.; Morandi L.; Romorini A.; Voit T.; Orstavik K.H.; Merlini L.; Trevisan C.; Biancalana V.; Housmanowa-Petrusewicz I.; Bione S.; Ricotti R.; Schwartz K.; Bonne G.; Toniolo D.;
Am. J. Hum. Genet. 66:1407-1412(2000)
Cited for: VARIANTS EDMD2 TYR-222; GLN-249; GLN-336; TRP-453; THR-469; PRO-527 AND LYS-528;

Clinical and molecular genetic spectrum of autosomal dominant Emery-Dreifuss muscular dystrophy due to mutations of the lamin A/C gene.
Bonne G.; Mercuri E.; Muchir A.; Urtizberea A.; Becane H.M.; Recan D.; Merlini L.; Wehnert M.; Boor R.; Reuner U.; Vorgerd M.; Wicklein E.M.; Eymard B.; Duboc D.; Penisson-Besnier I.; Cuisset J.M.; Ferrer X.; Desguerre I.; Lacombe D.; Bushby K.; Pollitt C.; Toniolo D.; Fardeau M.; Schwartz K.; Muntoni F.;
Ann. Neurol. 48:170-180(2000)
Cited for: VARIANTS EDMD2 CYS-45; PRO-50; SER-63; GLU-112 DEL; PRO-222; GLU-232; GLN-249; LYS-261 DEL; PRO-294; LYS-358; LYS-371; LYS-386; TRP-453; LYS-456; SER-520; PRO-527 AND LYS-528;

Novel and recurrent mutations in lamin A/C in patients with Emery-Dreifuss muscular dystrophy.
Brown C.A.; Lanning R.W.; McKinney K.Q.; Salvino A.R.; Cherniske E.; Crowe C.A.; Darras B.T.; Gominak S.; Greenberg C.R.; Grosmann C.; Heydemann P.; Mendell J.R.; Pober B.R.; Sasaki T.; Shapiro F.; Simpson D.A.; Suchowersky O.; Spence J.E.;
Am. J. Med. Genet. 102:359-367(2001)
Cited for: VARIANTS EDMD2 PRO-25; THR-43; SER-50; PRO-133; 196-ARG--THR-199 DELINS SER; GLN-249; LYS-261 DEL; LYS-358; TRP-453; ILE-456; PRO-527 AND HIS-624;

Identification of lamin A/C (LMNA) gene mutations in Korean patients with autosomal dominant Emery-Dreifuss muscular dystrophy and limb-girdle muscular dystrophy 1B.
Ki C.-S.; Hong J.S.; Jeong G.-Y.; Ahn K.J.; Choi K.-M.; Kim D.-K.; Kim J.-W.;
J. Hum. Genet. 47:225-228(2002)
Cited for: VARIANT EDMD2 GLN-249; VARIANT LGMD1B LEU-377;

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;

Clinical relevance of atrial fibrillation/flutter, stroke, pacemaker implant, and heart failure in Emery-Dreifuss muscular dystrophy: a long-term longitudinal study.
Boriani G.; Gallina M.; Merlini L.; Bonne G.; Toniolo D.; Amati S.; Biffi M.; Martignani C.; Frabetti L.; Bonvicini M.; Rapezzi C.; Branzi A.;
Stroke 34:901-908(2003)
Cited for: VARIANTS EDMD2 ASN-63; PRO-140; GLN-249; LEU-377; LYS-386 AND PRO-527;

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;

Novel LMNA mutations in patients with Emery-Dreifuss muscular dystrophy and functional characterization of four LMNA mutations.
Scharner J.; Brown C.A.; Bower M.; Iannaccone S.T.; Khatri I.A.; Escolar D.; Gordon E.; Felice K.; Crowe C.A.; Grosmann C.; Meriggioli M.N.; Asamoah A.; Gordon O.; Gnocchi V.F.; Ellis J.A.; Mendell J.R.; Zammit P.S.;
Hum. Mutat. 32:152-167(2011)
Cited for: VARIANTS EDMD2 SER-39; CYS-45; PRO-150; PRO-189; ARG-190 INS; LEU-206; TRP-249; GLN-249; PRO-268; PRO-271; PRO-294; PRO-295; PRO-303; GLN-355 DEL; LYS-358; LYS-361; LYS-386; ASP-449; TRP-453; PRO-454; TYR-461; ARG-467; PRO-527; LYS-528; ARG-528; SER-541; PRO-541; SER-602 AND CYS-644; CHARACTERIZATION OF VARIANTS EDMD2 PRO-25; TRP-249; ILE-456 AND PRO-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.