mutation t@sting

Prediction

polymorphism

Model: without_aae, prob: 9.88010123251116e-11 (classification due to TGP/ExAC, real probability is shown anyway) (explain)

Summary

homozygous in TGP or ExAC
known disease mutation at this position (HGMD CM032948)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr1:66036441A>GN/A show variant in all transcripts IGV

HGNC symbol

LEPR

Ensembl transcript ID

ENST00000406510

Genbank transcript ID

N/A

UniProt peptide

P48357

alteration type

single base exchange

alteration region

5'UTR

DNA changes

cDNA.443A>G
g.150194A>G

AA changes

N/A

position(s) of altered AA
if AA alteration in CDS

N/A

frameshift

N/A

known variant

Reference ID: rs1137100

database	homozygous (G/G)	heterozygous	allele carriers
1000G	420	764	1184
ExAC	6499	19769	26268

known disease mutation at this position, please check HGMD for details (HGMD ID CM032948)

regulatory features

H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
H3K4me1, Histone, Histone 3 Lysine 4 Mono-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	0.84	0.965
	1.443	0.925
(flanking)	0.346	0.602

explain score(s) and/or inspect your position(s) in in UCSC Genome Browser

splice sites

splice site change before start ATG (at aa -100) |

effect	gDNA position	score	detection sequence	exon-intron border
Donor increased	150188	wt: 0.23 / mu: 0.99	wt: CATTGAAGGAAAGAC mu: CATTGAAGGAAGGAC	TTGA\|agga

distance from splice site

Kozak consensus sequence altered?

conservation
protein level for non-synonymous changes

N/A

protein features

start (aa)	end (aa)	feature	details
1	21	SIGNAL		might get lost (downstream of altered splice site)
22	839	TOPO_DOM	Extracellular (Potential).	might get lost (downstream of altered splice site)
23	23	CARBOHYD	N-linked (GlcNAc...).	might get lost (downstream of altered splice site)
37	37	DISULFID		might get lost (downstream of altered splice site)
41	41	CARBOHYD	N-linked (GlcNAc...).	might get lost (downstream of altered splice site)
56	56	CARBOHYD	N-linked (GlcNAc...).	might get lost (downstream of altered splice site)
73	73	CARBOHYD	N-linked (GlcNAc...).	might get lost (downstream of altered splice site)
81	81	CARBOHYD	N-linked (GlcNAc...).	might get lost (downstream of altered splice site)
85	85	CONFLICT	T -> A (in Ref. 3; AAC50509/AAC50510/ AAC50511).	might get lost (downstream of altered splice site)
89	89	DISULFID		might get lost (downstream of altered splice site)
90	90	DISULFID		might get lost (downstream of altered splice site)
98	98	CARBOHYD	N-linked (GlcNAc...).	might get lost (downstream of altered splice site)
99	99	DISULFID		might get lost (downstream of altered splice site)
131	131	DISULFID		might get lost (downstream of altered splice site)
142	142	DISULFID		might get lost (downstream of altered splice site)
186	186	DISULFID		might get lost (downstream of altered splice site)
187	187	CARBOHYD	N-linked (GlcNAc...).	might get lost (downstream of altered splice site)
188	188	DISULFID		might get lost (downstream of altered splice site)
193	193	DISULFID		might get lost (downstream of altered splice site)
196	196	DISULFID		might get lost (downstream of altered splice site)
206	206	CARBOHYD	N-linked (GlcNAc...).	might get lost (downstream of altered splice site)
237	330	DOMAIN	Fibronectin type-III 1.	might get lost (downstream of altered splice site)
276	276	CARBOHYD	N-linked (GlcNAc...).	might get lost (downstream of altered splice site)
331	429	DOMAIN	Ig-like.	might get lost (downstream of altered splice site)
347	347	CARBOHYD	N-linked (GlcNAc...).	might get lost (downstream of altered splice site)
352	352	DISULFID		might get lost (downstream of altered splice site)
397	397	CARBOHYD	N-linked (GlcNAc...).	might get lost (downstream of altered splice site)
412	412	DISULFID		might get lost (downstream of altered splice site)
413	413	DISULFID		might get lost (downstream of altered splice site)
418	418	DISULFID		might get lost (downstream of altered splice site)
435	438	STRAND		might get lost (downstream of altered splice site)
436	436	DISULFID		might get lost (downstream of altered splice site)
445	449	STRAND		might get lost (downstream of altered splice site)
447	447	DISULFID		might get lost (downstream of altered splice site)
461	468	STRAND		might get lost (downstream of altered splice site)
467	484	REGION	Leptin-binding (Probable).	might get lost (downstream of altered splice site)
473	473	DISULFID		might get lost (downstream of altered splice site)
484	486	STRAND		might get lost (downstream of altered splice site)
488	488	DISULFID		might get lost (downstream of altered splice site)
488	490	STRAND		might get lost (downstream of altered splice site)
496	500	STRAND		might get lost (downstream of altered splice site)
498	498	DISULFID		might get lost (downstream of altered splice site)
509	516	STRAND		might get lost (downstream of altered splice site)
516	516	CARBOHYD	N-linked (GlcNAc...).	might get lost (downstream of altered splice site)
527	529	STRAND		might get lost (downstream of altered splice site)
528	528	DISULFID		might get lost (downstream of altered splice site)
531	534	HELIX		might get lost (downstream of altered splice site)
537	631	DOMAIN	Fibronectin type-III 2.	might get lost (downstream of altered splice site)
544	548	STRAND		might get lost (downstream of altered splice site)
549	552	TURN		might get lost (downstream of altered splice site)
553	557	STRAND		might get lost (downstream of altered splice site)
568	580	STRAND		might get lost (downstream of altered splice site)
584	588	STRAND		might get lost (downstream of altered splice site)
595	598	STRAND		might get lost (downstream of altered splice site)
607	615	STRAND		might get lost (downstream of altered splice site)
622	626	MOTIF	WSXWS motif.	might get lost (downstream of altered splice site)
624	624	CARBOHYD	N-linked (GlcNAc...).	might get lost (downstream of altered splice site)
639	732	DOMAIN	Fibronectin type-III 3.	might get lost (downstream of altered splice site)
659	659	CARBOHYD	N-linked (GlcNAc...).	might get lost (downstream of altered splice site)
688	688	CARBOHYD	N-linked (GlcNAc...).	might get lost (downstream of altered splice site)
697	697	CARBOHYD	N-linked (GlcNAc...).	might get lost (downstream of altered splice site)
728	728	CARBOHYD	N-linked (GlcNAc...).	might get lost (downstream of altered splice site)
734	829	DOMAIN	Fibronectin type-III 4.	might get lost (downstream of altered splice site)
750	750	CARBOHYD	N-linked (GlcNAc...).	might get lost (downstream of altered splice site)
840	862	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
863	1165	TOPO_DOM	Cytoplasmic (Potential).	might get lost (downstream of altered splice site)
871	879	MOTIF	Box 1 motif.	might get lost (downstream of altered splice site)
893	898	REGION	Required for JAK2 activation (By similarity).	might get lost (downstream of altered splice site)
976	976	CONFLICT	D -> A (in Ref. 1; AAA93015 and 4; AAB09673).	might get lost (downstream of altered splice site)
986	986	MUTAGEN	Y->F: Greatly reduced PTPN11 binding; no PTPN11 phosphorylation; no effect on STAT3 phosphorylation.	might get lost (downstream of altered splice site)
986	986	MOD_RES	Phosphotyrosine; by JAK2 (By similarity).	might get lost (downstream of altered splice site)
1078	1079	MUTAGEN	YY->FF: No effect on PTPN11 nor STAT3 phosphorylation.	might get lost (downstream of altered splice site)
1141	1141	MUTAGEN	Y->F: No effect on PTPN11 phosphorylation; no STAT3 phosphorylation.	might get lost (downstream of altered splice site)
1141	1141	MOD_RES	Phosphotyrosine; by JAK2 (By similarity).	might get lost (downstream of altered splice site)

length of protein

N/A

AA sequence altered

N/A

position of stopcodon in wt / mu CDS

N/A

position (AA) of stopcodon in wt / mu AA sequence

N/A

position of stopcodon in wt / mu cDNA

N/A

poly(A) signal

N/A

conservation
nucleotide level for all changes - no scoring up to now

N/A

position of start ATG in wt / mu cDNA

738 / 738

chromosome

strand

last intron/exon boundary

612

theoretical NMD boundary in CDS

cannot be calculated, too little distance between start ATG and last intron/exon boundary

length of CDS

699

coding sequence (CDS) position

N/A

cDNA position
(for ins/del: last normal base / first normal base)

443

gDNA position
(for ins/del: last normal base / first normal base)

150194

chromosomal position
(for ins/del: last normal base / first normal base)

66036441

original gDNA sequence snippet

TGCAGACAACATTGAAGGAAAGACATTTGTTTCAACAGTAA

altered gDNA sequence snippet

TGCAGACAACATTGAAGGAAGGACATTTGTTTCAACAGTAA

original cDNA sequence snippet

TGCAGACAACATTGAAGGAAAGACATTTGTTTCAACAGTAA

altered cDNA sequence snippet

TGCAGACAACATTGAAGGAAGGACATTTGTTTCAACAGTAA

wildtype AA sequence

MMPTTVVSLL STTDLEKGSV CISDQFNSVN FSEAEGTEVT YEDESQRQPF VKYATLISNS
KPSETGEEQG LINSSVTKCF SSKNSPLKDS FSNSSWEIEA QAFFILSDQH PNIISPHLTF
SEGLDELLKL EGNFPEENND KKSIYYLGVT SIKKRESGVL LTDKSRVSCP FPAPCLFTDI
RVLQDSCSHF VENNINLGTS SKKTFASYMP QFQTCSTQTH KIMENKMCDL TV*

mutated AA sequence

N/A

speed

0.60 s

All positions are in basepairs (bp) if not explicitly stated differently.
AA/aa: amino acid; CDS: coding sequence; mu: mutated; NMD: nonsense-mediated mRNA decay; nt: nucleotide; wt: wildtype; TGP: 1000 Genomes Project