Yum, tasty mutations...

mutation t@sting

 documentation

Prediction

disease causing

 Model: simple_aae, prob: 0.99563295963017 (classification due to ClinVar, real probability is shown anyway)      (explain)
Summary
  • amino acid sequence changed
  • known disease mutation at this position (HGMD CM091531)
  • known disease mutation: rs18106 (pathogenic)
  • protein features (might be) affected
  • splice site changes
 hyperlink
analysed issue analysis result
name of alteration no title
alteration (phys. location) chr21:27269931G>AN/A show variant in all transcripts   IGV
HGNC symbol APP
Ensembl transcript ID ENST00000439274
Genbank transcript ID NM_001136130
UniProt peptide P05067
alteration type single base exchange
alteration region CDS
DNA changes c.1850C>T
cDNA.1884C>T
g.273516C>T
AA changes A617V Score: 64 explain score(s)
position(s) of altered AA
if AA alteration in CDS		 617
frameshift no
known variant Reference ID: rs193922916
Allele 'A' was neither found in ExAC nor 1000G.
known disease mutation: rs18106 (pathogenic for Alzheimer disease) dbSNP  NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM091531)

known disease mutation at this position, please check HGMD for details (HGMD ID CM091531)
known disease mutation at this position, please check HGMD for details (HGMD ID CM091531)
regulatory features H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
H3K9me1, Histone, Histone 3 Lysine 9 mono-methylation
H4K20me1, Histone, Histone 4 Lysine 20 mono-methylation
H3K4me1, Histone, Histone 3 Lysine 4 Mono-Methylation
phyloP / phastCons
PhyloPPhastCons
(flanking)-1.2820.428
3.4880.997
(flanking)2.3691
explain score(s) and/or inspect your position(s) in in UCSC Genome Browser
splice sites
effectgDNA positionscorewt detection sequence exon-intron border
Donor increased273509wt: 0.35 / mu: 0.93wt: TGAAGATGGATGCAG
mu: TGAAGATGGATGTAG		 AAGA|tgga
distance from splice site 47
Kozak consensus sequence altered? N/A
conservation
protein level for non-synonymous changes
speciesmatchgeneaaalignment
Human      617KTEEISEVKMDAEFRHDSGYEVHH
mutated  not conserved    617KTEEISEVKMDVEFRHDSGYEVH
Ptroglodytes  all identical  ENSPTRG00000013811  673KTEEISEVKMDAEFRHDSGYEVH
Mmulatta  all identical  ENSMMUG00000014384  673KTEEISEVKMDAEFRHDSGYEVH
Fcatus  all identical  ENSFCAG00000001556  654EISEVKMDAEFRHESGYEVH
Mmusculus  all identical  ENSMUSG00000022892  598KTEEISEVKMDAEFGHDSGFEVR
Ggallus  all identical  ENSGALG00000015770  654AEFRHDSGYEVH
Trubripes  not conserved  ENSTRUG00000010470  667ETEDRQSTEYEVH
Drerio  not conserved  ENSDARG00000055543  658---EIPKVRLDIEERHNAGYDVR
Dmelanogaster  no alignment  FBgn0000108  n/a
Celegans  not conserved  C42D8.8  564EDKNIKELRVDIEPIID
Xtropicalis  all conserved  ENSXETG00000013612  674KTEEISEVKMDSEYRHDAAYEVH
protein features
start (aa)end (aa)featuredetails 
18699TOPO_DOMExtracellular (Potential).lost
623623CARBOHYDO-linked (GalNAc...).might get lost (downstream of altered splice site)
628628CARBOHYDO-linked (GalNAc...).might get lost (downstream of altered splice site)
633633CARBOHYDO-linked (GalNAc...).might get lost (downstream of altered splice site)
647647CONFLICTD -> E (in Ref. 35; AAA51722).might get lost (downstream of altered splice site)
651651CARBOHYDO-linked (GalNAc...).might get lost (downstream of altered splice site)
652652CARBOHYDO-linked (GalNAc...).might get lost (downstream of altered splice site)
656656MUTAGENS->A: Abolishes chondroitin sulfate binding in L-APP733 isoform.might get lost (downstream of altered splice site)
656656CARBOHYDO-linked (Xyl...) (chondroitin sulfate); in L-APP isoforms.might get lost (downstream of altered splice site)
659659CARBOHYDO-linked (GalNAc...).might get lost (downstream of altered splice site)
663663CARBOHYDO-linked (GalNAc...) (Probable).might get lost (downstream of altered splice site)
667667CARBOHYDO-linked (GalNAc...) (Probable).might get lost (downstream of altered splice site)
671672SITECleavage; by beta-secretase.might get lost (downstream of altered splice site)
672673SITECleavage; by caspase-6; when associated with variant 670-N-L-671.might get lost (downstream of altered splice site)
674677TURNmight get lost (downstream of altered splice site)
676676MUTAGENR->G: 60-70% zinc-induced beta-APP (28) peptide aggregation.might get lost (downstream of altered splice site)
677677METALCopper or zinc 2.might get lost (downstream of altered splice site)
679679CARBOHYDO-linked (GalNAc...).might get lost (downstream of altered splice site)
679682STRANDmight get lost (downstream of altered splice site)
681681MUTAGENY->F: 60-70% zinc-induced beta-APP (28) peptide aggregation.might get lost (downstream of altered splice site)
681681METALCopper or zinc 2 (Probable).might get lost (downstream of altered splice site)
683685STRANDmight get lost (downstream of altered splice site)
684684METALCopper or zinc 2.might get lost (downstream of altered splice site)
684684MUTAGENH->R: Only 23% zinc-induced beta-APP (28) peptide aggregation.might get lost (downstream of altered splice site)
685685METALCopper or zinc 2.might get lost (downstream of altered splice site)
687688SITECleavage; by alpha-secretase.might get lost (downstream of altered splice site)
688691STRANDmight get lost (downstream of altered splice site)
688711PEPTIDEP3(40). /FTId=PRO_0000000096.might get lost (downstream of altered splice site)
688713PEPTIDEP3(42). /FTId=PRO_0000000095.might get lost (downstream of altered splice site)
690691SITECleavage; by theta-secretase.might get lost (downstream of altered splice site)
695697HELIXmight get lost (downstream of altered splice site)
697697CARBOHYDO-linked (GalNAc...).might get lost (downstream of altered splice site)
698700STRANDmight get lost (downstream of altered splice site)
700723TRANSMEMHelical; (Potential).might get lost (downstream of altered splice site)
702705STRANDmight get lost (downstream of altered splice site)
704704MUTAGENG->V: Reduced protein oxidation. No hippocampal neuron toxicity.might get lost (downstream of altered splice site)
704704SITEImplicated in free radical propagation (By similarity).might get lost (downstream of altered splice site)
706706MUTAGENM->V: No free radical production. No hippocampal neuron toxicity.might get lost (downstream of altered splice site)
706706MUTAGENM->L: Reduced lipid peroxidation inhibition.might get lost (downstream of altered splice site)
706706SITESusceptible to oxidation.might get lost (downstream of altered splice site)
707712STRANDmight get lost (downstream of altered splice site)
711712SITECleavage; by gamma-secretase; site 1.might get lost (downstream of altered splice site)
713714SITECleavage; by gamma-secretase; site 2.might get lost (downstream of altered splice site)
717717MUTAGENV->K: Decreased beta-APP42/total APP-beta ratio.might get lost (downstream of altered splice site)
717717MUTAGENV->F,G,I: Increased beta-APP42/beta-APP40 ratio.might get lost (downstream of altered splice site)
717717MUTAGENV->M: Increased beta-APP42/beta-APP40 ratio. No change in apoptosis after caspase cleavage.might get lost (downstream of altered splice site)
717717MUTAGENV->C,S: Unchanged beta-APP42/total APP- beta ratio.might get lost (downstream of altered splice site)
720721SITECleavage; by gamma-secretase; site 3.might get lost (downstream of altered splice site)
724724CONFLICTMissing (in Ref. 22; AAB26263/AAB26264).might get lost (downstream of altered splice site)
724734MOTIFBasolateral sorting signal.might get lost (downstream of altered splice site)
724770TOPO_DOMCytoplasmic (Potential).might get lost (downstream of altered splice site)
728728MUTAGENY->A: No effect on APBA1 nor APBB1 binding. Greatly reduces the binding to APPBP2. APP internalization unchanged. No change in beta-APP42 secretion.might get lost (downstream of altered splice site)
729729MOD_RESPhosphothreonine (By similarity).might get lost (downstream of altered splice site)
730730MOD_RESPhosphoserine; by APP-kinase I (By similarity).might get lost (downstream of altered splice site)
731731CONFLICTI -> N (in Ref. 22; AAB26263/AAB26264/ AAB26265).might get lost (downstream of altered splice site)
732751REGIONInteraction with G(o)-alpha.might get lost (downstream of altered splice site)
739739MUTAGEND->N: No effect on FADD-induced apoptosis.might get lost (downstream of altered splice site)
739739MUTAGEND->A: No cleavage by caspases during apoptosis.might get lost (downstream of altered splice site)
739740SITECleavage; by caspase-6, caspase-8 or caspase-9.might get lost (downstream of altered splice site)
743743MUTAGENT->E: Reduced NGF-stimulated neurite extension. No effect on APP maturation.might get lost (downstream of altered splice site)
743743MOD_RESPhosphothreonine; by CDK5 and MAPK10.might get lost (downstream of altered splice site)
743743MUTAGENT->A: Greatly reduces the binding to SHC1 and APBB family members; no effect on NGF-stimulated neurite extension.might get lost (downstream of altered splice site)
744754HELIXmight get lost (downstream of altered splice site)
755758STRANDmight get lost (downstream of altered splice site)
756756MUTAGENG->A: APP internalization unchanged. No change in beta-APP42 secretion.might get lost (downstream of altered splice site)
757757MUTAGENY->A: Little APP internalization. Reduced beta-APP42 secretion.might get lost (downstream of altered splice site)
757757MOD_RESPhosphotyrosine; by ABL1 (By similarity).might get lost (downstream of altered splice site)
757757CONFLICTY -> S (in Ref. 30; AAA35540).might get lost (downstream of altered splice site)
757757MUTAGENY->G: Loss of binding to MAPK8IP1, APBA1, APBB1, APPBP2 and SHC1.might get lost (downstream of altered splice site)
757757MOD_RESPhosphotyrosine.might get lost (downstream of altered splice site)
759759MUTAGENN->A: No binding to APBA1, no effect on APBB1 binding. Little APP internalization. Reduced beta-APP42 secretion.might get lost (downstream of altered splice site)
759762MOTIFNPXY motif; contains endocytosis signal.might get lost (downstream of altered splice site)
760760MUTAGENP->A: Little APP internalization. Reduced beta-APP42 secretion.might get lost (downstream of altered splice site)
762762MUTAGENY->A: Loss of binding to APBA1 and APBB1. APP internalization unchanged. No change in beta-APP42 secretion.might get lost (downstream of altered splice site)
762762MOD_RESPhosphotyrosine.might get lost (downstream of altered splice site)
763765STRANDmight get lost (downstream of altered splice site)
length of protein normal
AA sequence altered yes
position of stopcodon in wt / mu CDS 2145 / 2145
position (AA) of stopcodon in wt / mu AA sequence 715 / 715
position of stopcodon in wt / mu cDNA 2179 / 2179
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 35 / 35
chromosome 21
strand -1
last intron/exon boundary 2078
theoretical NMD boundary in CDS 1993
length of CDS 2145
coding sequence (CDS) position 1850
cDNA position
(for ins/del: last normal base / first normal base)		 1884
gDNA position
(for ins/del: last normal base / first normal base)		 273516
chromosomal position
(for ins/del: last normal base / first normal base)		 27269931
original gDNA sequence snippet CTCTGAAGTGAAGATGGATGCAGAATTCCGACATGACTCAG
altered gDNA sequence snippet CTCTGAAGTGAAGATGGATGTAGAATTCCGACATGACTCAG
original cDNA sequence snippet CTCTGAAGTGAAGATGGATGCAGAATTCCGACATGACTCAG
altered cDNA sequence snippet CTCTGAAGTGAAGATGGATGTAGAATTCCGACATGACTCAG
wildtype AA sequence MLPGLALLLL AAWTARALEV YPELQITNVV EANQPVTIQN WCKRGRKQCK THPHFVIPYR
CLVGEFVSDA LLVPDKCKFL HQERMDVCET HLHWHTVAKE TCSEKSTNLH DYGMLLPCGI
DKFRGVEFVC CPLAEESDNV DSADAEEDDS DVWWGGADTD YADGSEDKVV EVAEEEEVAE
VEEEEADDDE DDEDGDEVEE EAEEPYEEAT ERTTSIATTT TTTTESVEEV VREVCSEQAE
TGPCRAMISR WYFDVTEGKC APFFYGGCGG NRNNFDTEEY CMAVCGSAMS QSLLKTTQEP
LARDPVKLPT TAASTPDAVD KYLETPGDEN EHAHFQKAKE RLEAKHRERM SQVMREWEEA
ERQAKNLPKA DKKAVIQHFQ EKVESLEQEA ANERQQLVET HMARVEAMLN DRRRLALENY
ITALQAVPPR PRHVFNMLKK YVRAEQKDRQ HTLKHFEHVR MVDPKKAAQI RSQVMTHLRV
IYERMNQSLS LLYNVPAVAE EIQDEVDELL QKEQNYSDDV LANMISEPRI SYGNDALMPS
LTETKTTVEL LPVNGEFSLD DLQPWHSFGA DSVPANTENE VEPVDARPAA DRGLTTRPGS
GLTNIKTEEI SEVKMDAEFR HDSGYEVHHQ KLVFFAEDVG SNKGAIIGLM VGGVVIATVI
VITLVMLKKK QYTSIHHGVV EVDAAVTPEE RHLSKMQQNG YENPTYKFFE QMQN*
mutated AA sequence MLPGLALLLL AAWTARALEV YPELQITNVV EANQPVTIQN WCKRGRKQCK THPHFVIPYR
CLVGEFVSDA LLVPDKCKFL HQERMDVCET HLHWHTVAKE TCSEKSTNLH DYGMLLPCGI
DKFRGVEFVC CPLAEESDNV DSADAEEDDS DVWWGGADTD YADGSEDKVV EVAEEEEVAE
VEEEEADDDE DDEDGDEVEE EAEEPYEEAT ERTTSIATTT TTTTESVEEV VREVCSEQAE
TGPCRAMISR WYFDVTEGKC APFFYGGCGG NRNNFDTEEY CMAVCGSAMS QSLLKTTQEP
LARDPVKLPT TAASTPDAVD KYLETPGDEN EHAHFQKAKE RLEAKHRERM SQVMREWEEA
ERQAKNLPKA DKKAVIQHFQ EKVESLEQEA ANERQQLVET HMARVEAMLN DRRRLALENY
ITALQAVPPR PRHVFNMLKK YVRAEQKDRQ HTLKHFEHVR MVDPKKAAQI RSQVMTHLRV
IYERMNQSLS LLYNVPAVAE EIQDEVDELL QKEQNYSDDV LANMISEPRI SYGNDALMPS
LTETKTTVEL LPVNGEFSLD DLQPWHSFGA DSVPANTENE VEPVDARPAA DRGLTTRPGS
GLTNIKTEEI SEVKMDVEFR HDSGYEVHHQ KLVFFAEDVG SNKGAIIGLM VGGVVIATVI
VITLVMLKKK QYTSIHHGVV EVDAAVTPEE RHLSKMQQNG YENPTYKFFE QMQN*
speed 1.07 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