Variant VAR_017658 | SNPeffect 4.0

Phenotypic summary of VAR_017658

Compact overview of VAR_017658
UniProt ID	Gene	Mutation	Mutation type	Disease	OMIM	dbSNP
LMNA_HUMAN	LMNA	L140R	Disease	Hutchinson-Gilford progeria syndrome (HGPS)	176670	rs60652225

Short stretch summary of VAR_017658
Predictor	Predicted regions overview	Comparison to WT	Stretches in variant	Stretches in WT
Tango		0 No change	3	3
Waltz		0 No change	1	1
Limbo		0 No change	10	10
Domain composition of LMNA_HUMAN
Database	Domain composition	Residue details
PFAM		Filament (Residues 30-386), IF_tail (Residues 425-540)

TANGO aggregation

Graphical comparison of TANGO regions in variant and wild type
Protein	Predicted regions overview	TANGO regions	Total score
Variant		3	1044
Wild type		3	1044

TANGO regions in wild type and variant
Wild type TANGO regions
N-term gatekeepers	TANGO region	C-term gatekeepers	Start	End	Score
ELNDR	LAVYI	DRVRS	42	46	90
LKAGQ	VVTIWAA	GAGAT	494	500	75
RKLVR	SVTVV	EDDED	546	550	10
Variant protein TANGO regions
N-term gatekeepers	TANGO region	C-term gatekeepers	Start	End	Score
ELNDR	LAVYI	DRVRS	42	46	90
LKAGQ	VVTIWAA	GAGAT	494	500	75
RKLVR	SVTVV	EDDED	546	550	10

Difference in TANGO aggregation between wild type and variant
	This graph plots the per-residue TANGO aggregation score difference between the wild type protein and this variant. From left to right, all residue TANGO score differences from the N-terminus to the C-terminus are plotted. A flat line indicates that the variant does not alter the aggregation profile of the protein. Positive peaks indicate increased aggregation tendency due to this variant. Negative peaks indicate decreased aggregation tendency due to this variant.

Difference in TANGO aggregation between wild type and variant

This graph plots the per-residue TANGO aggregation score difference between the wild type protein and this variant.
From left to right, all residue TANGO score differences from the N-terminus to the C-terminus are plotted.
A flat line indicates that the variant does not alter the aggregation profile of the protein.
Positive peaks indicate increased aggregation tendency due to this variant.
Negative peaks indicate decreased aggregation tendency due to this variant.

TANGO aggregation profile score plot
	This graph plots the per-residue TANGO aggregation score of the variant protein. From left to right, all residue scores from the N-terminus to the C-terminus are plotted

WALTZ amylogenicity

Graphical comparison of WALTZ regions in variant and wild type
Protein	Predicted regions overview	WALTZ regions	Total score
Variant		1	430
Wild type		1	430

WALTZ regions in wild type and variant
Wild type WALTZ regions
N-term gatekeepers	WALTZ region	C-term gatekeepers	Start	End	Score
ELNDR	LAVYID	RVRSL	42	47	66
Variant protein WALTZ regions
N-term gatekeepers	WALTZ region	C-term gatekeepers	Start	End	Score
ELNDR	LAVYID	RVRSL	42	47	66

Difference in WALTZ amylogenicity between wild type and variant
	This graph plots the per-residue WALTZ amylogenic score difference between the wild type protein and this variant. From left to right, all residue WALTZ score differences from the N-terminus to the C-terminus are plotted. A flat line indicates that the variant does not alter the amylogenic profile of the protein. Positive peaks indicate increased amylogenic tendency due to this variant. Negative peaks indicate decreased amylogenic tendency due to this variant.

Difference in WALTZ amylogenicity between wild type and variant

This graph plots the per-residue WALTZ amylogenic score difference between the wild type protein and this variant.
From left to right, all residue WALTZ score differences from the N-terminus to the C-terminus are plotted.
A flat line indicates that the variant does not alter the amylogenic profile of the protein.
Positive peaks indicate increased amylogenic tendency due to this variant.
Negative peaks indicate decreased amylogenic tendency due to this variant.

WALTZ amylogenic profile score plot
	This graph plots the per-residue WALTZ amylogenic score of the variant protein. From left to right, all residue scores from the N-terminus to the C-terminus are plotted

LIMBO chaperone binding

Graphical comparison of LIMBO regions in variant and wild type
Protein	Predicted regions overview	LIMBO regions	Total score
Variant		10	5926
Wild type		10	5926

LIMBO regions in wild type and variant
Wild type LIMBO regions
N-term gatekeepers	WALTZ region	C-term gatekeepers	Start	End	Score
TENAG	LRLRITES	EEVVS	59	66	97
VREEF	KELKARNT	KKEGD	114	121	48
KKQLQ	DEMLRRVD	AENRL	185	192	41
RVDAE	NRLQTMKE	ELDFQ	195	202	57
VEQYK	KELEKTYS	AKLDN	261	268	88
LSQLQ	KQLAAKEA	KLRDL	311	318	7
ERDTS	RRLLAEKE	REMAE	335	342	71
EGEEE	RLRLSPSPT	SQRSR	386	394	85
LKAGQ	VVTIWAAG	AGATH	494	501	100
LVTRS	YLLGNSSP	RTQSP	646	653	100
Variant protein LIMBO regions
N-term gatekeepers	WALTZ region	C-term gatekeepers	Start	End	Score
TENAG	LRLRITES	EEVVS	59	66	97
VREEF	KELKARNT	KKEGD	114	121	48
KKQLQ	DEMLRRVD	AENRL	185	192	41
RVDAE	NRLQTMKE	ELDFQ	195	202	57
VEQYK	KELEKTYS	AKLDN	261	268	88
LSQLQ	KQLAAKEA	KLRDL	311	318	7
ERDTS	RRLLAEKE	REMAE	335	342	71
EGEEE	RLRLSPSPT	SQRSR	386	394	85
LKAGQ	VVTIWAAG	AGATH	494	501	100
LVTRS	YLLGNSSP	RTQSP	646	653	100

Difference in LIMBO chaperone binding between wild type and variant
	This graph plots the per-residue LIMBO chaperone binding difference between the wild type protein and this variant. From left to right, all residue LIMBO score differences from the N-terminus to the C-terminus are plotted. A flat line indicates that the variant does not alter the chaperone binding profile of the protein. Positive peaks indicate increased predicted chaperone binding due to this variant. Negative peaks indicate decreased predicted chaperone binding due to this variant.

Difference in LIMBO chaperone binding between wild type and variant

This graph plots the per-residue LIMBO chaperone binding difference between the wild type protein and this variant.
From left to right, all residue LIMBO score differences from the N-terminus to the C-terminus are plotted.
A flat line indicates that the variant does not alter the chaperone binding profile of the protein.
Positive peaks indicate increased predicted chaperone binding due to this variant.
Negative peaks indicate decreased predicted chaperone binding due to this variant.

LIMBO chaperone binding score plot
	This graph plots the per-residue LIMBO chaperone binding score of the variant protein. From left to right, all residue scores from the N-terminus to the C-terminus are plotted

FOLDX structural profile

There is currently no structural information available to make the required analyses.

Functional sites, structural features and cellular processing

Functional sites and structural features
Feature	This residue
Catalytic site	No
Secondary structure	No secondary structure information available
Transmembrane topology	No TM regions in this protein

Cellular processing
Feature	Affected by variant
Signal peptide	No
Farnesylation anchor	No
N-Myristoylation anchor	No
Geranylgeranyl transferase Type 1 anchor	No
Geranylgeranyl transferase Type 2 anchor	No
Glycosylphosphatidylinositol (GPI) anchor	No
Peroxisomal targeting signal PTS1	No
Subcellular location	No

All mutations from LMNA_HUMAN

118 mutations listed

Variant	UniProt ID	Mutation	Disease	Mutation Type	dTANGO	dWALTZ	dLIMBO	ddG
VAR_009971	LMNA_HUMAN	Y45C	Emery-Dreifuss muscular dystrophy type 2 (EDMD2)	Disease	-274	-393	0	N.A.
VAR_009974	LMNA_HUMAN	I63S	Emery-Dreifuss muscular dystrophy type 2 (EDMD2)	Disease	0	0	-296	N.A.
VAR_009975	LMNA_HUMAN	L85R	Cardiomyopathy dilated type 1A (CMD1A)	Disease	0	0	0	N.A.
VAR_009972	LMNA_HUMAN	R50P	Emery-Dreifuss muscular dystrophy type 2 (EDMD2)	Disease	0	0	0	N.A.
VAR_009977	LMNA_HUMAN	N195K	Cardiomyopathy dilated type 1A (CMD1A)	Disease	0	0	9	N.A.
VAR_009982	LMNA_HUMAN	Q294P	Emery-Dreifuss muscular dystrophy type 2 (EDMD2)	Disease	0	0	0	N.A.
VAR_009980	LMNA_HUMAN	R249Q	Emery-Dreifuss muscular dystrophy type 2 (EDMD2)	Disease	0	0	0	N.A.
VAR_009979	LMNA_HUMAN	H222Y	Emery-Dreifuss muscular dystrophy type 2 (EDMD2)	Disease	0	0	-4	N.A.
VAR_009984	LMNA_HUMAN	R343Q	Emery-Dreifuss muscular dystrophy type 2 (EDMD2)	Disease	0	0	0	N.A.
VAR_009985	LMNA_HUMAN	E358K	Emery-Dreifuss muscular dystrophy type 2 (EDMD2)	Disease	0	0	0	N.A.
VAR_009986	LMNA_HUMAN	M371K	Emery-Dreifuss muscular dystrophy type 2 (EDMD2)	Disease	7	0	8	N.A.
VAR_009987	LMNA_HUMAN	R386K	Emery-Dreifuss muscular dystrophy type 2 (EDMD2)	Disease	0	0	-230	N.A.
VAR_009990	LMNA_HUMAN	I469T	Emery-Dreifuss muscular dystrophy type 2 (EDMD2)	Disease	0	0	0	3.65
VAR_009991	LMNA_HUMAN	R482L	Familial partial lipodystrophy type 2 (FPLD2)	Disease	41	1	0	0.03
VAR_009989	LMNA_HUMAN	G465D	Familial partial lipodystrophy type 2 (FPLD2)	Disease	0	0	0	1.51
VAR_009992	LMNA_HUMAN	R482Q	Familial partial lipodystrophy type 2 (FPLD2)	Disease	0	0	0	0.36
VAR_009993	LMNA_HUMAN	R482W	Familial partial lipodystrophy type 2 (FPLD2)	Disease	64	6	-1	0.16
VAR_009994	LMNA_HUMAN	K486N	Familial partial lipodystrophy type 2 (FPLD2)	Disease	0	0	0	0.77
VAR_009997	LMNA_HUMAN	L530P	Emery-Dreifuss muscular dystrophy type 2 (EDMD2)	Disease	0	-5	5	7.69
VAR_009985	LMNA_HUMAN	E358K	Muscular dystrophy congenital LMNA-related (CMD-LMNA)	Disease	0	0	0	N.A.
VAR_009972	LMNA_HUMAN	R50P	Muscular dystrophy congenital LMNA-related (CMD-LMNA)	Disease	0	0	0	N.A.
VAR_009983	LMNA_HUMAN	R336Q	Emery-Dreifuss muscular dystrophy type 2 (EDMD2)	Disease	0	0	-114	N.A.
VAR_009995	LMNA_HUMAN	R527P	Familial partial lipodystrophy type 2 (FPLD2)	Disease	0	-4	7	2.75
VAR_009978	LMNA_HUMAN	E203G	Cardiomyopathy dilated type 1A (CMD1A)	Disease	0	0	0	N.A.
VAR_009996	LMNA_HUMAN	T528K	Emery-Dreifuss muscular dystrophy type 2 (EDMD2)	Disease	0	-5	-6	9.78