UniProtKB/SwissProt variant VAR

Prelamin-A/C
Gene: LMNA
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Variant information Variant position:

377 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

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 EDMD2; no obvious effect on nuclear morphology in cultured skin fibroblasts from heterozygous patients; no effect on protein level. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs61672878 [ dbSNP | Ensembl ]

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                       DEYQELLDIKLALDMEINAYRKLLEGEEERLRLSPSPSSQR

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.

Type	Positions	Description
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; by CDK1
Modified residue	395 – 395	Phosphoserine; by ATR
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)
Mutagenesis	358 – 358	E -> K. Loss of interaction with IFFO1.
Mutagenesis	373 – 373	I -> E. Impaired lamin assembly.
Mutagenesis	375 – 375	A -> D. Impaired lamin assembly.
Mutagenesis	377 – 377	R -> HP. Impaired lamin assembly.
Mutagenesis	381 – 381	E -> K. Impaired lamin assembly.
Mutagenesis	384 – 384	E -> K. Impaired lamin assembly.
Mutagenesis	386 – 386	R -> M. Loss of interaction with IFFO1.
Mutagenesis	386 – 386	R -> VLP. Impaired lamin assembly.
Mutagenesis	390 – 390	S -> A. Decreased localization to the nucleoplasm during interphase.
Mutagenesis	392 – 392	S -> A. Impaired disassembly of the nuclear envelope during mitosis. Strongly decreased disassembly of the nuclear envelope during mitosis; when associates with A-22. Decreased localization to the nucleoplasm during interphase. Impaired disassembly of the micronuclear envelope in response to genome instability.
Mutagenesis	392 – 392	S -> D. Mimics phosphorylation; increased localization to the nucleoplasm during interphase. Causes redistribution between the nucleus and the cytoplasm during interphase; when associated with D-22 and D-628.
Mutagenesis	395 – 395	S -> A. Impaired phosphorylation by ATR in response to genome instability leading ro decreased phosphorylation by CDK1.
Mutagenesis	395 – 395	S -> D. Mimics phosphorylation; disassembly of the micronuclear envelope in response to genome instability.

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 EDMD2 LYS-208 DEL AND HIS-377; FUNCTION; 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 EDMD2 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; Nuclear envelope alterations in fibroblasts from patients with muscular dystrophy, cardiomyopathy, and partial lipodystrophy carrying lamin A/C gene mutations.
Muchir A.; Medioni J.; Laluc M.; Massart C.; Arimura T.; van der Kooi A.J.; Desguerre I.; Mayer M.; Ferrer X.; Briault S.; Hirano M.; Worman H.J.; Mallet A.; Wehnert M.; Schwartz K.; Bonne G.;
Muscle Nerve 30:444-450(2004)
Cited for: SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS EDMD2 LYS-32 DEL; SER-63; GLN-249; LYS-358; CYS-401; TRP-453 AND PRO-527; CHARACTERIZATION OF VARIANTS EDMD2 LYS-208 DEL AND HIS-377; CHARACTERIZATION OF VARIANT FPLD2 LEU-482; CHARACTERIZATION OF VARIANT CMD1A CYS-541; 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 EDMD2 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 EDMD2 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.

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P02545: Variant p.Arg377His