UniProtKB/Swiss-Prot P02545: Variant p.Val415Ile

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

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

US 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 Valine (V) to Isoleucine (I) at position 415 (V415I, p.Val415Ile). 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:

Similar physico-chemical property. Both residues are medium size and hydrophobic. 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
Variant description:

Rare variant; found in patients with atrial fibrillation; uncertain significance; no effect on nuclear lamin A localization; enhances the interaction with SYNE2; causes nuclear deformations in heat shock experiments. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs267607606 [ dbSNP | Ensembl ]

Sequence information Variant position:

415 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:

SQRSRGRASSHSSQTQGGGS V TKKRKLESTESRSSFSQHAR 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                         SQRSRGRASSHSSQTQGGGSVTKKRKLEST------ESR-SSFSQHAR

Mouse                         SQRSRGRASSHSSQSQGGGSVTKKRKLESS------ESR-S

Rat                           SQRSRGRASSHSSQSQGGGSVTKKRKLESS------ESR-S

Pig                           SQRSRGRASSHSSQTQSGGSVTKKRKLESS------ESR-S

Chicken                       SQRG---ARSSGLQHSGAGS-AKKRRLEDGEGREGREGR-T

Xenopus laevis                TQKRSARTIASHSGAHISSSASKRRRLEEG------ESRSS

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
Region	384 – 664	Tail
Region	384 – 442	Disordered
Compositional bias	391 – 417	Polar residues
Modified residue	395 – 395	Phosphoserine; by ATR
Modified residue	398 – 398	Phosphoserine
Modified residue	403 – 403	Phosphoserine
Modified residue	404 – 404	Phosphoserine
Modified residue	406 – 406	Phosphoserine
Modified residue	407 – 407	Phosphoserine
Modified residue	414 – 414	Phosphoserine
Modified residue	416 – 416	Phosphothreonine
Modified residue	423 – 423	Phosphoserine
Modified residue	426 – 426	Phosphoserine
Modified residue	429 – 429	Phosphoserine
Modified residue	431 – 431	Phosphoserine
Cross	417 – 417	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Cross	420 – 420	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
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
Comprehensive mutation scanning of LMNA in 268 patients with lone atrial fibrillation.
Brauch K.M.; Chen L.Y.; Olson T.M.;
Am. J. Cardiol. 103:1426-1428(2009)
Cited for: VARIANTS SER-125; ILE-415 AND PRO-488; Mutations in LMNA modulate the lamin A--Nesprin-2 interaction and cause LINC complex alterations.
Yang L.; Munck M.; Swamvdinathan K.; Kapinos L.E.; Noegel A.A.; Neumann S.;
PLoS ONE 8:E71850-E71850(2013)
Cited for: CHARACTERIZATION OF VARIANTS CYS-401; ASP-411; CYS-413; ILE-415; CYS-419; PRO-421 AND GLY-427; INTERACTION WITH SYNE2;

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.