Yum, tasty mutations...

MutationTaster - study a chromosomal position

 MTQE documentation
NEVER press reload or F5 - unless you want to start from the very beginning.
input seems to be ok - now mapping the variant to the different transcripts...
found 9 transcript(s)...
Querying Taster for transcript #1: ENST00000346798
Querying Taster for transcript #2: ENST00000354192
Querying Taster for transcript #3: ENST00000348990
Querying Taster for transcript #4: ENST00000357903
Querying Taster for transcript #5: ENST00000439274
Querying Taster for transcript #6: ENST00000358918
Querying Taster for transcript #7: ENST00000359726
Querying Taster for transcript #8: ENST00000440126
Querying Taster for transcript #9: ENST00000448388
MT speed 0 s - this script 5.249621 s

Results

genesymbolpredictionprobabilitymodelprediction
problem		splicingClinVaramino acid changesvariant typedbSNP IDprotein lengthfile
APPdisease_causing_automatic0.999999680590359simple_aaeaffected0A617Gsingle base exchangers63750671show file
APPdisease_causing_automatic0.999999680590359simple_aaeaffected0A636Gsingle base exchangers63750671show file
APPdisease_causing_automatic0.999999680590359simple_aaeaffected0A636Gsingle base exchangers63750671show file
APPdisease_causing_automatic0.999999680590359simple_aaeaffected0A668Gsingle base exchangers63750671show file
APPdisease_causing_automatic0.999999680590359simple_aaeaffected0A582Gsingle base exchangers63750671show file
APPdisease_causing_automatic0.999999798195631simple_aaeaffected0A692Gsingle base exchangers63750671show file
APPdisease_causing_automatic0.999999936808366simple_aaeaffected0A674Gsingle base exchangers63750671show file
APPdisease_causing_automatic0.999999947590514simple_aaeaffected0A561Gsingle base exchangers63750671show file
APPdisease_causing_automatic0.99999999992583simple_aaeaffected0A673Gsingle base exchangers63750671show file

Taster files

Yum, tasty mutations...

mutation t@sting

 documentation

Prediction

disease causing

 Model: simple_aae, prob: 0.999999680590359 (classification due to ClinVar, real probability is shown anyway)      (explain)
Summary
  • amino acid sequence changed
  • known disease mutation at this position (HGMD CM920065)
  • known disease mutation: rs18091 (pathogenic)
  • protein features (might be) affected
  • splice site changes
 hyperlink
analysed issue analysis result
name of alteration no title
alteration (phys. location) chr21:27264170G>CN/A show variant in all transcripts   IGV
HGNC symbol APP
Ensembl transcript ID ENST00000348990
Genbank transcript ID NM_201414
UniProt peptide P05067
alteration type single base exchange
alteration region CDS
DNA changes c.1850C>G
cDNA.1997C>G
g.279277C>G
AA changes A617G Score: 60 explain score(s)
position(s) of altered AA
if AA alteration in CDS		 617
frameshift no
known variant Reference ID: rs63750671
Allele 'C' was neither found in ExAC nor 1000G.
known disease mutation: rs18091 (pathogenic for Alzheimer disease|Alzheimer disease, type 1|ABetaA21G amyloidosis|not provided) dbSNP  NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM920065)

known disease mutation at this position, please check HGMD for details (HGMD ID CM920065)
known disease mutation at this position, please check HGMD for details (HGMD ID CM920065)
regulatory features H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
phyloP / phastCons
PhyloPPhastCons
(flanking)-2.20.042
4.0560.998
(flanking)2.9711
explain score(s) and/or inspect your position(s) in in UCSC Genome Browser
splice sites
effectgDNA positionscorewt detection sequence exon-intron border
Acc marginally increased279267wt: 0.3597 / mu: 0.3618 (marginal change - not scored)wt: TTTCTTAATTTGTTTTCAAGGTGTTCTTTGCAGAAGATGTG
mu: TTTCTTAATTTGTTTTCAAGGTGTTCTTTGGAGAAGATGTG		 aagg|TGTT
Donor marginally increased279276wt: 0.9493 / mu: 0.9953 (marginal change - not scored)wt: TCTTTGCAGAAGATG
mu: TCTTTGGAGAAGATG		 TTTG|caga
Donor marginally increased279279wt: 0.6197 / mu: 0.6710 (marginal change - not scored)wt: TTGCAGAAGATGTGG
mu: TTGGAGAAGATGTGG		 GCAG|aaga
Acc gained2792760.35mu: TTGTTTTCAAGGTGTTCTTTGGAGAAGATGTGGGTTCAAAC tttg|GAGA
Donor gained2792730.53mu: TGTTCTTTGGAGAAG TTCT|ttgg
distance from splice site 11
Kozak consensus sequence altered? N/A
conservation
protein level for non-synonymous changes
speciesmatchgeneaaalignment
Human      617YEVHHQKLVFFAEDVGSNKGAIIG
mutated  not conserved    617YEVHHQKLVFFGEDVGSNKGAII
Ptroglodytes  all identical  ENSPTRG00000013811  692YEVHHQKLVFFAEDVGSNKGAII
Mmulatta  all identical  ENSMMUG00000014384  692YEVHHQKLVFFAEDVGSNKGAII
Fcatus  all identical  ENSFCAG00000001556  673YEVHHQKLVFFAEDVGSNKGAII
Mmusculus  all identical  ENSMUSG00000022892  617FEVRHQKLVFFAEDVGSNKGAII
Ggallus  all identical  ENSGALG00000015770  673YEVHHQKLVFFAEDVGSNKGAII
Trubripes  all identical  ENSTRUG00000010470  686YEVHHQKLVFFAEDVGSNKGAII
Drerio  all identical  ENSDARG00000055543  673YDVRDKRLMFLAEDMGSNKGAII
Dmelanogaster  no alignment  FBgn0000108  n/a
Celegans  not conserved  C42D8.8  609ASFYRHDKLIQSPEVERSASSVFQ
Xtropicalis  all identical  ENSXETG00000013612  693YEVHHQKLVFFAEEVGSNKGAII
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 2088 / 2088
position (AA) of stopcodon in wt / mu AA sequence 696 / 696
position of stopcodon in wt / mu cDNA 2235 / 2235
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 148 / 148
chromosome 21
strand -1
last intron/exon boundary 2134
theoretical NMD boundary in CDS 1936
length of CDS 2088
coding sequence (CDS) position 1850
cDNA position
(for ins/del: last normal base / first normal base)		 1997
gDNA position
(for ins/del: last normal base / first normal base)		 279277
chromosomal position
(for ins/del: last normal base / first normal base)		 27264170
original gDNA sequence snippet TGTTTTCAAGGTGTTCTTTGCAGAAGATGTGGGTTCAAACA
altered gDNA sequence snippet TGTTTTCAAGGTGTTCTTTGGAGAAGATGTGGGTTCAAACA
original cDNA sequence snippet TCAAAAATTGGTGTTCTTTGCAGAAGATGTGGGTTCAAACA
altered cDNA sequence snippet TCAAAAATTGGTGTTCTTTGGAGAAGATGTGGGTTCAAACA
wildtype AA sequence MLPGLALLLL AAWTARALEV PTDGNAGLLA EPQIAMFCGR LNMHMNVQNG KWDSDPSGTK
TCIDTKEGIL QYCQEVYPEL QITNVVEANQ PVTIQNWCKR GRKQCKTHPH FVIPYRCLVG
EFVSDALLVP DKCKFLHQER MDVCETHLHW HTVAKETCSE KSTNLHDYGM LLPCGIDKFR
GVEFVCCPLA EESDNVDSAD AEEDDSDVWW GGADTDYADG SEDKVVEVAE EEEVAEVEEE
EADDDEDDED GDEVEEEAEE PYEEATERTT SIATTTTTTT ESVEEVVRVP TTAASTPDAV
DKYLETPGDE NEHAHFQKAK ERLEAKHRER MSQVMREWEE AERQAKNLPK ADKKAVIQHF
QEKVESLEQE AANERQQLVE THMARVEAML NDRRRLALEN YITALQAVPP RPRHVFNMLK
KYVRAEQKDR QHTLKHFEHV RMVDPKKAAQ IRSQVMTHLR VIYERMNQSL SLLYNVPAVA
EEIQDEVDEL LQKEQNYSDD VLANMISEPR ISYGNDALMP SLTETKTTVE LLPVNGEFSL
DDLQPWHSFG ADSVPANTEN EVEPVDARPA ADRGLTTRPG SGLTNIKTEE ISEVKMDAEF
RHDSGYEVHH QKLVFFAEDV GSNKGAIIGL MVGGVVIATV IVITLVMLKK KQYTSIHHGV
VEVDAAVTPE ERHLSKMQQN GYENPTYKFF EQMQN*
mutated AA sequence MLPGLALLLL AAWTARALEV PTDGNAGLLA EPQIAMFCGR LNMHMNVQNG KWDSDPSGTK
TCIDTKEGIL QYCQEVYPEL QITNVVEANQ PVTIQNWCKR GRKQCKTHPH FVIPYRCLVG
EFVSDALLVP DKCKFLHQER MDVCETHLHW HTVAKETCSE KSTNLHDYGM LLPCGIDKFR
GVEFVCCPLA EESDNVDSAD AEEDDSDVWW GGADTDYADG SEDKVVEVAE EEEVAEVEEE
EADDDEDDED GDEVEEEAEE PYEEATERTT SIATTTTTTT ESVEEVVRVP TTAASTPDAV
DKYLETPGDE NEHAHFQKAK ERLEAKHRER MSQVMREWEE AERQAKNLPK ADKKAVIQHF
QEKVESLEQE AANERQQLVE THMARVEAML NDRRRLALEN YITALQAVPP RPRHVFNMLK
KYVRAEQKDR QHTLKHFEHV RMVDPKKAAQ IRSQVMTHLR VIYERMNQSL SLLYNVPAVA
EEIQDEVDEL LQKEQNYSDD VLANMISEPR ISYGNDALMP SLTETKTTVE LLPVNGEFSL
DDLQPWHSFG ADSVPANTEN EVEPVDARPA ADRGLTTRPG SGLTNIKTEE ISEVKMDAEF
RHDSGYEVHH QKLVFFGEDV GSNKGAIIGL MVGGVVIATV IVITLVMLKK KQYTSIHHGV
VEVDAAVTPE ERHLSKMQQN GYENPTYKFF EQMQN*
speed 0.36 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
back to results table
Yum, tasty mutations...

mutation t@sting

 documentation

Prediction

disease causing

 Model: simple_aae, prob: 0.999999680590359 (classification due to ClinVar, real probability is shown anyway)      (explain)
Summary
  • amino acid sequence changed
  • known disease mutation at this position (HGMD CM920065)
  • known disease mutation: rs18091 (pathogenic)
  • protein features (might be) affected
  • splice site changes
 hyperlink
analysed issue analysis result
name of alteration no title
alteration (phys. location) chr21:27264170G>CN/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.1907C>G
cDNA.1941C>G
g.279277C>G
AA changes A636G Score: 60 explain score(s)
position(s) of altered AA
if AA alteration in CDS		 636
frameshift no
known variant Reference ID: rs63750671
Allele 'C' was neither found in ExAC nor 1000G.
known disease mutation: rs18091 (pathogenic for Alzheimer disease|Alzheimer disease, type 1|ABetaA21G amyloidosis|not provided) dbSNP  NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM920065)

known disease mutation at this position, please check HGMD for details (HGMD ID CM920065)
known disease mutation at this position, please check HGMD for details (HGMD ID CM920065)
regulatory features H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
phyloP / phastCons
PhyloPPhastCons
(flanking)-2.20.042
4.0560.998
(flanking)2.9711
explain score(s) and/or inspect your position(s) in in UCSC Genome Browser
splice sites
effectgDNA positionscorewt detection sequence exon-intron border
Acc marginally increased279267wt: 0.3597 / mu: 0.3618 (marginal change - not scored)wt: TTTCTTAATTTGTTTTCAAGGTGTTCTTTGCAGAAGATGTG
mu: TTTCTTAATTTGTTTTCAAGGTGTTCTTTGGAGAAGATGTG		 aagg|TGTT
Donor marginally increased279276wt: 0.9493 / mu: 0.9953 (marginal change - not scored)wt: TCTTTGCAGAAGATG
mu: TCTTTGGAGAAGATG		 TTTG|caga
Donor marginally increased279279wt: 0.6197 / mu: 0.6710 (marginal change - not scored)wt: TTGCAGAAGATGTGG
mu: TTGGAGAAGATGTGG		 GCAG|aaga
Acc gained2792760.35mu: TTGTTTTCAAGGTGTTCTTTGGAGAAGATGTGGGTTCAAAC tttg|GAGA
Donor gained2792730.53mu: TGTTCTTTGGAGAAG TTCT|ttgg
distance from splice site 11
Kozak consensus sequence altered? N/A
conservation
protein level for non-synonymous changes
speciesmatchgeneaaalignment
Human      636YEVHHQKLVFFAEDVGSNKGAIIG
mutated  not conserved    636YEVHHQKLVFFGEDVGSNKGAII
Ptroglodytes  all identical  ENSPTRG00000013811  692YEVHHQKLVFFAEDVGSNKGAII
Mmulatta  all identical  ENSMMUG00000014384  692YEVHHQKLVFFAEDVGSNKGAII
Fcatus  all identical  ENSFCAG00000001556  673YEVHHQKLVFFAEDVGSNKGAII
Mmusculus  all identical  ENSMUSG00000022892  617FEVRHQKLVFFAEDVGSNKGAII
Ggallus  all identical  ENSGALG00000015770  673YEVHHQKLVFFAEDVGSNKGAII
Trubripes  all identical  ENSTRUG00000010470  686YEVHHQKLVFFAEDVGSNKGAII
Drerio  all identical  ENSDARG00000055543  677YDVRDKRLMFLAEDMGSNKGAII
Dmelanogaster  no alignment  FBgn0000108  n/a
Celegans  not conserved  C42D8.8  609ASFYRHDKLIQSPEVERSASSVFQ
Xtropicalis  all identical  ENSXETG00000013612  693YEVHHQKLVFFAEEVGSNKGAII
protein features
start (aa)end (aa)featuredetails 
18699TOPO_DOMExtracellular (Potential).lost
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)
656656CARBOHYDO-linked (Xyl...) (chondroitin sulfate); in L-APP isoforms.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)
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)
681681METALCopper or zinc 2 (Probable).might 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)
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)
704704SITEImplicated in free radical propagation (By similarity).might get lost (downstream of altered splice site)
704704MUTAGENG->V: Reduced protein oxidation. No hippocampal neuron toxicity.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)
706706SITESusceptible to oxidation.might get lost (downstream of altered splice site)
706706MUTAGENM->L: Reduced lipid peroxidation inhibition.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->C,S: Unchanged 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)
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)
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)
743743MUTAGENT->E: Reduced NGF-stimulated neurite extension. No effect on APP maturation.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)
757757MOD_RESPhosphotyrosine.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)
757757MUTAGENY->G: Loss of binding to MAPK8IP1, APBA1, APBB1, APPBP2 and SHC1.might get lost (downstream of altered splice site)
757757CONFLICTY -> S (in Ref. 30; AAA35540).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)
762762MOD_RESPhosphotyrosine.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)
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 1907
cDNA position
(for ins/del: last normal base / first normal base)		 1941
gDNA position
(for ins/del: last normal base / first normal base)		 279277
chromosomal position
(for ins/del: last normal base / first normal base)		 27264170
original gDNA sequence snippet TGTTTTCAAGGTGTTCTTTGCAGAAGATGTGGGTTCAAACA
altered gDNA sequence snippet TGTTTTCAAGGTGTTCTTTGGAGAAGATGTGGGTTCAAACA
original cDNA sequence snippet TCAAAAATTGGTGTTCTTTGCAGAAGATGTGGGTTCAAACA
altered cDNA sequence snippet TCAAAAATTGGTGTTCTTTGGAGAAGATGTGGGTTCAAACA
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 SEVKMDAEFR HDSGYEVHHQ KLVFFGEDVG SNKGAIIGLM VGGVVIATVI
VITLVMLKKK QYTSIHHGVV EVDAAVTPEE RHLSKMQQNG YENPTYKFFE QMQN*
speed 0.87 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
back to results table
Yum, tasty mutations...

mutation t@sting

 documentation

Prediction

disease causing

 Model: simple_aae, prob: 0.999999680590359 (classification due to ClinVar, real probability is shown anyway)      (explain)
Summary
  • amino acid sequence changed
  • known disease mutation at this position (HGMD CM920065)
  • known disease mutation: rs18091 (pathogenic)
  • protein features (might be) affected
  • splice site changes
 hyperlink
analysed issue analysis result
name of alteration no title
alteration (phys. location) chr21:27264170G>CN/A show variant in all transcripts   IGV
HGNC symbol APP
Ensembl transcript ID ENST00000359726
Genbank transcript ID N/A
UniProt peptide P05067
alteration type single base exchange
alteration region CDS
DNA changes c.1907C>G
cDNA.2107C>G
g.279277C>G
AA changes A636G Score: 60 explain score(s)
position(s) of altered AA
if AA alteration in CDS		 636
frameshift no
known variant Reference ID: rs63750671
Allele 'C' was neither found in ExAC nor 1000G.
known disease mutation: rs18091 (pathogenic for Alzheimer disease|Alzheimer disease, type 1|ABetaA21G amyloidosis|not provided) dbSNP  NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM920065)

known disease mutation at this position, please check HGMD for details (HGMD ID CM920065)
known disease mutation at this position, please check HGMD for details (HGMD ID CM920065)
regulatory features H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
phyloP / phastCons
PhyloPPhastCons
(flanking)-2.20.042
4.0560.998
(flanking)2.9711
explain score(s) and/or inspect your position(s) in in UCSC Genome Browser
splice sites
effectgDNA positionscorewt detection sequence exon-intron border
Acc marginally increased279267wt: 0.3597 / mu: 0.3618 (marginal change - not scored)wt: TTTCTTAATTTGTTTTCAAGGTGTTCTTTGCAGAAGATGTG
mu: TTTCTTAATTTGTTTTCAAGGTGTTCTTTGGAGAAGATGTG		 aagg|TGTT
Donor marginally increased279276wt: 0.9493 / mu: 0.9953 (marginal change - not scored)wt: TCTTTGCAGAAGATG
mu: TCTTTGGAGAAGATG		 TTTG|caga
Donor marginally increased279279wt: 0.6197 / mu: 0.6710 (marginal change - not scored)wt: TTGCAGAAGATGTGG
mu: TTGGAGAAGATGTGG		 GCAG|aaga
Acc gained2792760.35mu: TTGTTTTCAAGGTGTTCTTTGGAGAAGATGTGGGTTCAAAC tttg|GAGA
Donor gained2792730.53mu: TGTTCTTTGGAGAAG TTCT|ttgg
distance from splice site 11
Kozak consensus sequence altered? N/A
conservation
protein level for non-synonymous changes
speciesmatchgeneaaalignment
Human      636YEVHHQKLVFFAEDVGSNKGAIIG
mutated  not conserved    636YEVHHQKLVFFGEDVGSNKGAII
Ptroglodytes  all identical  ENSPTRG00000013811  692YEVHHQKLVFFAEDVGSNKGAII
Mmulatta  all identical  ENSMMUG00000014384  692YEVHHQKLVFFAEDVGSNKGAII
Fcatus  all identical  ENSFCAG00000001556  673YEVHHQKLVFFAEDVGSNKGAII
Mmusculus  all identical  ENSMUSG00000022892  617FEVRHQKLVFFAEDVGSNKGAII
Ggallus  all identical  ENSGALG00000015770  673YEVHHQKLVFFAEDVGSNKGAII
Trubripes  all identical  ENSTRUG00000010470  686YEVHHQKLVFFAEDVGSNKGAII
Drerio  all identical  ENSDARG00000055543  673YDVRDKRLMFLAEDMGSNKGAII
Dmelanogaster  no alignment  FBgn0000108  n/a
Celegans  not conserved  C42D8.8  599ASFYRHDKLIQSPEVE
Xtropicalis  all identical  ENSXETG00000013612  693YEVHHQKLVFFAEEVGSNKGAII
protein features
start (aa)end (aa)featuredetails 
18699TOPO_DOMExtracellular (Potential).lost
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)
656656CARBOHYDO-linked (Xyl...) (chondroitin sulfate); in L-APP isoforms.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)
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)
681681METALCopper or zinc 2 (Probable).might 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)
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)
704704SITEImplicated in free radical propagation (By similarity).might get lost (downstream of altered splice site)
704704MUTAGENG->V: Reduced protein oxidation. No hippocampal neuron toxicity.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)
706706SITESusceptible to oxidation.might get lost (downstream of altered splice site)
706706MUTAGENM->L: Reduced lipid peroxidation inhibition.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->C,S: Unchanged 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)
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)
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)
743743MUTAGENT->E: Reduced NGF-stimulated neurite extension. No effect on APP maturation.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)
757757MOD_RESPhosphotyrosine.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)
757757MUTAGENY->G: Loss of binding to MAPK8IP1, APBA1, APBB1, APPBP2 and SHC1.might get lost (downstream of altered splice site)
757757CONFLICTY -> S (in Ref. 30; AAA35540).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)
762762MOD_RESPhosphotyrosine.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)
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 2345 / 2345
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 201 / 201
chromosome 21
strand -1
last intron/exon boundary 2244
theoretical NMD boundary in CDS 1993
length of CDS 2145
coding sequence (CDS) position 1907
cDNA position
(for ins/del: last normal base / first normal base)		 2107
gDNA position
(for ins/del: last normal base / first normal base)		 279277
chromosomal position
(for ins/del: last normal base / first normal base)		 27264170
original gDNA sequence snippet TGTTTTCAAGGTGTTCTTTGCAGAAGATGTGGGTTCAAACA
altered gDNA sequence snippet TGTTTTCAAGGTGTTCTTTGGAGAAGATGTGGGTTCAAACA
original cDNA sequence snippet TCAAAAATTGGTGTTCTTTGCAGAAGATGTGGGTTCAAACA
altered cDNA sequence snippet TCAAAAATTGGTGTTCTTTGGAGAAGATGTGGGTTCAAACA
wildtype AA sequence MLPGLALLLL AAWTARALEV PTDGNAGLLA EPQIAMFCGR LNMHMNVQNG KWDSDPSGTK
TCIDTKEGIL QYCQEVYPEL QITNVVEANQ PVTIQNWCKR GRKQCKTHPH FVIPYRCLVG
EFVSDALLVP DKCKFLHQER MDVCETHLHW HTVAKETCSE KSTNLHDYGM LLPCGIDKFR
GVEFVCCPLA EESDNVDSAD AEEDDSDVWW GGADTDYADG SEDKVVEVAE EEEVAEVEEE
EADDDEDDED GDEVEEEAEE PYEEATERTT SIATTTTTTT ESVEEVVRVS 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 PTDGNAGLLA EPQIAMFCGR LNMHMNVQNG KWDSDPSGTK
TCIDTKEGIL QYCQEVYPEL QITNVVEANQ PVTIQNWCKR GRKQCKTHPH FVIPYRCLVG
EFVSDALLVP DKCKFLHQER MDVCETHLHW HTVAKETCSE KSTNLHDYGM LLPCGIDKFR
GVEFVCCPLA EESDNVDSAD AEEDDSDVWW GGADTDYADG SEDKVVEVAE EEEVAEVEEE
EADDDEDDED GDEVEEEAEE PYEEATERTT SIATTTTTTT ESVEEVVRVS 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 KLVFFGEDVG SNKGAIIGLM VGGVVIATVI
VITLVMLKKK QYTSIHHGVV EVDAAVTPEE RHLSKMQQNG YENPTYKFFE QMQN*
speed 0.31 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
back to results table
Yum, tasty mutations...

mutation t@sting

 documentation

Prediction

disease causing

 Model: simple_aae, prob: 0.999999680590359 (classification due to ClinVar, real probability is shown anyway)      (explain)
Summary
  • amino acid sequence changed
  • known disease mutation at this position (HGMD CM920065)
  • known disease mutation: rs18091 (pathogenic)
  • protein features (might be) affected
  • splice site changes
 hyperlink
analysed issue analysis result
name of alteration no title
alteration (phys. location) chr21:27264170G>CN/A show variant in all transcripts   IGV
HGNC symbol APP
Ensembl transcript ID ENST00000440126
Genbank transcript ID NM_001136016
UniProt peptide P05067
alteration type single base exchange
alteration region CDS
DNA changes c.2003C>G
cDNA.2160C>G
g.279277C>G
AA changes A668G Score: 60 explain score(s)
position(s) of altered AA
if AA alteration in CDS		 668
frameshift no
known variant Reference ID: rs63750671
Allele 'C' was neither found in ExAC nor 1000G.
known disease mutation: rs18091 (pathogenic for Alzheimer disease|Alzheimer disease, type 1|ABetaA21G amyloidosis|not provided) dbSNP  NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM920065)

known disease mutation at this position, please check HGMD for details (HGMD ID CM920065)
known disease mutation at this position, please check HGMD for details (HGMD ID CM920065)
regulatory features H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
phyloP / phastCons
PhyloPPhastCons
(flanking)-2.20.042
4.0560.998
(flanking)2.9711
explain score(s) and/or inspect your position(s) in in UCSC Genome Browser
splice sites
effectgDNA positionscorewt detection sequence exon-intron border
Acc marginally increased279267wt: 0.3597 / mu: 0.3618 (marginal change - not scored)wt: TTTCTTAATTTGTTTTCAAGGTGTTCTTTGCAGAAGATGTG
mu: TTTCTTAATTTGTTTTCAAGGTGTTCTTTGGAGAAGATGTG		 aagg|TGTT
Donor marginally increased279276wt: 0.9493 / mu: 0.9953 (marginal change - not scored)wt: TCTTTGCAGAAGATG
mu: TCTTTGGAGAAGATG		 TTTG|caga
Donor marginally increased279279wt: 0.6197 / mu: 0.6710 (marginal change - not scored)wt: TTGCAGAAGATGTGG
mu: TTGGAGAAGATGTGG		 GCAG|aaga
Acc gained2792760.35mu: TTGTTTTCAAGGTGTTCTTTGGAGAAGATGTGGGTTCAAAC tttg|GAGA
Donor gained2792730.53mu: TGTTCTTTGGAGAAG TTCT|ttgg
distance from splice site 11
Kozak consensus sequence altered? N/A
conservation
protein level for non-synonymous changes
speciesmatchgeneaaalignment
Human      668YEVHHQKLVFFAEDVGSNKGAIIG
mutated  not conserved    668HQKLVFFGEDVGSNKGAII
Ptroglodytes  all identical  ENSPTRG00000013811  692YEVHHQKLVFFAEDVGSNKGAII
Mmulatta  all identical  ENSMMUG00000014384  692YEVHHQKLVFFAEDVGSNKGAII
Fcatus  all identical  ENSFCAG00000001556  673YEVHHQKLVFFAEDVGSNKGAII
Mmusculus  all identical  ENSMUSG00000022892  617FEVRHQKLVFFAEDVGSN
Ggallus  all identical  ENSGALG00000015770  673YEVHHQKLVFFAEDVG
Trubripes  all identical  ENSTRUG00000010470  686YEVHHQKLVFFAEDVGSNKGAII
Drerio  all identical  ENSDARG00000055543  673RDKRLMFLAEDMGSNKGAII
Dmelanogaster  no alignment  FBgn0000108  n/a
Celegans  not conserved  C42D8.8  618ASFYRHDKLIQSPEVER
Xtropicalis  all identical  ENSXETG00000013612  693YEVHHQKLVFFAEEVGSNKGAII
protein features
start (aa)end (aa)featuredetails 
18699TOPO_DOMExtracellular (Potential).lost
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)
706706SITESusceptible to oxidation.might get lost (downstream of altered splice site)
706706MUTAGENM->L: Reduced lipid peroxidation inhibition.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->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)
717717MUTAGENV->F,G,I: Increased beta-APP42/beta-APP40 ratio.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)
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->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)
743743MOD_RESPhosphothreonine; by CDK5 and MAPK10.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)
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)
757757CONFLICTY -> S (in Ref. 30; AAA35540).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)
757757MUTAGENY->G: Loss of binding to MAPK8IP1, APBA1, APBB1, APPBP2 and SHC1.might get lost (downstream of altered splice site)
757757MOD_RESPhosphotyrosine; by ABL1 (By similarity).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)
762762MOD_RESPhosphotyrosine.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)
763765STRANDmight get lost (downstream of altered splice site)
length of protein normal
AA sequence altered yes
position of stopcodon in wt / mu CDS 2241 / 2241
position (AA) of stopcodon in wt / mu AA sequence 747 / 747
position of stopcodon in wt / mu cDNA 2398 / 2398
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 158 / 158
chromosome 21
strand -1
last intron/exon boundary 2297
theoretical NMD boundary in CDS 2089
length of CDS 2241
coding sequence (CDS) position 2003
cDNA position
(for ins/del: last normal base / first normal base)		 2160
gDNA position
(for ins/del: last normal base / first normal base)		 279277
chromosomal position
(for ins/del: last normal base / first normal base)		 27264170
original gDNA sequence snippet TGTTTTCAAGGTGTTCTTTGCAGAAGATGTGGGTTCAAACA
altered gDNA sequence snippet TGTTTTCAAGGTGTTCTTTGGAGAAGATGTGGGTTCAAACA
original cDNA sequence snippet TCAAAAATTGGTGTTCTTTGCAGAAGATGTGGGTTCAAACA
altered cDNA sequence snippet TCAAAAATTGGTGTTCTTTGGAGAAGATGTGGGTTCAAACA
wildtype AA sequence MDQLEDLLVL FINYVPTDGN AGLLAEPQIA MFCGRLNMHM NVQNGKWDSD PSGTKTCIDT
KEGILQYCQE VYPELQITNV VEANQPVTIQ NWCKRGRKQC KTHPHFVIPY RCLVGEFVSD
ALLVPDKCKF LHQERMDVCE THLHWHTVAK ETCSEKSTNL HDYGMLLPCG IDKFRGVEFV
CCPLAEESDN VDSADAEEDD SDVWWGGADT DYADGSEDKV VEVAEEEEVA EVEEEEADDD
EDDEDGDEVE EEAEEPYEEA TERTTSIATT TTTTTESVEE VVREVCSEQA ETGPCRAMIS
RWYFDVTEGK CAPFFYGGCG GNRNNFDTEE YCMAVCGSAI PTTAASTPDA VDKYLETPGD
ENEHAHFQKA KERLEAKHRE RMSQVMREWE EAERQAKNLP KADKKAVIQH FQEKVESLEQ
EAANERQQLV ETHMARVEAM LNDRRRLALE NYITALQAVP PRPRHVFNML KKYVRAEQKD
RQHTLKHFEH VRMVDPKKAA QIRSQVMTHL RVIYERMNQS LSLLYNVPAV AEEIQDEVDE
LLQKEQNYSD DVLANMISEP RISYGNDALM PSLTETKTTV ELLPVNGEFS LDDLQPWHSF
GADSVPANTE NEVEPVDARP AADRGLTTRP GSGLTNIKTE EISEVKMDAE FRHDSGYEVH
HQKLVFFAED VGSNKGAIIG LMVGGVVIAT VIVITLVMLK KKQYTSIHHG VVEVDAAVTP
EERHLSKMQQ NGYENPTYKF FEQMQN*
mutated AA sequence MDQLEDLLVL FINYVPTDGN AGLLAEPQIA MFCGRLNMHM NVQNGKWDSD PSGTKTCIDT
KEGILQYCQE VYPELQITNV VEANQPVTIQ NWCKRGRKQC KTHPHFVIPY RCLVGEFVSD
ALLVPDKCKF LHQERMDVCE THLHWHTVAK ETCSEKSTNL HDYGMLLPCG IDKFRGVEFV
CCPLAEESDN VDSADAEEDD SDVWWGGADT DYADGSEDKV VEVAEEEEVA EVEEEEADDD
EDDEDGDEVE EEAEEPYEEA TERTTSIATT TTTTTESVEE VVREVCSEQA ETGPCRAMIS
RWYFDVTEGK CAPFFYGGCG GNRNNFDTEE YCMAVCGSAI PTTAASTPDA VDKYLETPGD
ENEHAHFQKA KERLEAKHRE RMSQVMREWE EAERQAKNLP KADKKAVIQH FQEKVESLEQ
EAANERQQLV ETHMARVEAM LNDRRRLALE NYITALQAVP PRPRHVFNML KKYVRAEQKD
RQHTLKHFEH VRMVDPKKAA QIRSQVMTHL RVIYERMNQS LSLLYNVPAV AEEIQDEVDE
LLQKEQNYSD DVLANMISEP RISYGNDALM PSLTETKTTV ELLPVNGEFS LDDLQPWHSF
GADSVPANTE NEVEPVDARP AADRGLTTRP GSGLTNIKTE EISEVKMDAE FRHDSGYEVH
HQKLVFFGED VGSNKGAIIG LMVGGVVIAT VIVITLVMLK KKQYTSIHHG VVEVDAAVTP
EERHLSKMQQ NGYENPTYKF FEQMQN*
speed 0.51 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
back to results table
Yum, tasty mutations...

mutation t@sting

 documentation

Prediction

disease causing

 Model: simple_aae, prob: 0.999999680590359 (classification due to ClinVar, real probability is shown anyway)      (explain)
Summary
  • amino acid sequence changed
  • known disease mutation at this position (HGMD CM920065)
  • known disease mutation: rs18091 (pathogenic)
  • protein features (might be) affected
  • splice site changes
 hyperlink
analysed issue analysis result
name of alteration no title
alteration (phys. location) chr21:27264170G>CN/A show variant in all transcripts   IGV
HGNC symbol APP
Ensembl transcript ID ENST00000448388
Genbank transcript ID NM_001136131
UniProt peptide P05067
alteration type single base exchange
alteration region CDS
DNA changes c.1745C>G
cDNA.1937C>G
g.279277C>G
AA changes A582G Score: 60 explain score(s)
position(s) of altered AA
if AA alteration in CDS		 582
frameshift no
known variant Reference ID: rs63750671
Allele 'C' was neither found in ExAC nor 1000G.
known disease mutation: rs18091 (pathogenic for Alzheimer disease|Alzheimer disease, type 1|ABetaA21G amyloidosis|not provided) dbSNP  NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM920065)

known disease mutation at this position, please check HGMD for details (HGMD ID CM920065)
known disease mutation at this position, please check HGMD for details (HGMD ID CM920065)
regulatory features H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
phyloP / phastCons
PhyloPPhastCons
(flanking)-2.20.042
4.0560.998
(flanking)2.9711
explain score(s) and/or inspect your position(s) in in UCSC Genome Browser
splice sites
effectgDNA positionscorewt detection sequence exon-intron border
Acc marginally increased279267wt: 0.3597 / mu: 0.3618 (marginal change - not scored)wt: TTTCTTAATTTGTTTTCAAGGTGTTCTTTGCAGAAGATGTG
mu: TTTCTTAATTTGTTTTCAAGGTGTTCTTTGGAGAAGATGTG		 aagg|TGTT
Donor marginally increased279276wt: 0.9493 / mu: 0.9953 (marginal change - not scored)wt: TCTTTGCAGAAGATG
mu: TCTTTGGAGAAGATG		 TTTG|caga
Donor marginally increased279279wt: 0.6197 / mu: 0.6710 (marginal change - not scored)wt: TTGCAGAAGATGTGG
mu: TTGGAGAAGATGTGG		 GCAG|aaga
Acc gained2792760.35mu: TTGTTTTCAAGGTGTTCTTTGGAGAAGATGTGGGTTCAAAC tttg|GAGA
Donor gained2792730.53mu: TGTTCTTTGGAGAAG TTCT|ttgg
distance from splice site 11
Kozak consensus sequence altered? N/A
conservation
protein level for non-synonymous changes
speciesmatchgeneaaalignment
Human      582YEVHHQKLVFFAEDVGSNKGAIIG
mutated  not conserved    582YEVHHQKLVFFGEDVGSNKGAII
Ptroglodytes  all identical  ENSPTRG00000013811  692YEVHHQKLVFFAEDV
Mmulatta  all identical  ENSMMUG00000014384  692YEVHHQKLVFFAEDV
Fcatus  all identical  ENSFCAG00000001556  673YEVHHQKLVFFAEDVGSNKGAII
Mmusculus  all identical  ENSMUSG00000022892  617FEVRHQKLVFFAEDVGSNKGAII
Ggallus  all identical  ENSGALG00000015770  673YEVHHQKLVFFAEDVGSNKGAII
Trubripes  all identical  ENSTRUG00000010470  689YEVHHQKLVFFAEDVGSNKGAII
Drerio  all identical  ENSDARG00000055543  683YDVRDKRLMFLAEDMGSNK
Dmelanogaster  no alignment  FBgn0000108  n/a
Celegans  not conserved  C42D8.8  609ASFYRHDKLIQSPEVERSASSVFQ
Xtropicalis  all identical  ENSXETG00000013612  693YEVHHQKLVFFAEEV
protein features
start (aa)end (aa)featuredetails 
18699TOPO_DOMExtracellular (Potential).lost
614614CARBOHYDO-linked (GalNAc...).might get lost (downstream of altered splice site)
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)
684684MUTAGENH->R: Only 23% zinc-induced beta-APP (28) peptide aggregation.might get lost (downstream of altered splice site)
684684METALCopper or zinc 2.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)
706706SITESusceptible to oxidation.might get lost (downstream of altered splice site)
706706MUTAGENM->L: Reduced lipid peroxidation inhibition.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)
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->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->K: Decreased beta-APP42/total APP-beta ratio.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->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)
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)
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)
757757CONFLICTY -> S (in Ref. 30; AAA35540).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)
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)
757757MOD_RESPhosphotyrosine; by ABL1 (By similarity).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 1983 / 1983
position (AA) of stopcodon in wt / mu AA sequence 661 / 661
position of stopcodon in wt / mu cDNA 2175 / 2175
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 193 / 193
chromosome 21
strand -1
last intron/exon boundary 2074
theoretical NMD boundary in CDS 1831
length of CDS 1983
coding sequence (CDS) position 1745
cDNA position
(for ins/del: last normal base / first normal base)		 1937
gDNA position
(for ins/del: last normal base / first normal base)		 279277
chromosomal position
(for ins/del: last normal base / first normal base)		 27264170
original gDNA sequence snippet TGTTTTCAAGGTGTTCTTTGCAGAAGATGTGGGTTCAAACA
altered gDNA sequence snippet TGTTTTCAAGGTGTTCTTTGGAGAAGATGTGGGTTCAAACA
original cDNA sequence snippet TCAAAAATTGGTGTTCTTTGCAGAAGATGTGGGTTCAAACA
altered cDNA sequence snippet TCAAAAATTGGTGTTCTTTGGAGAAGATGTGGGTTCAAACA
wildtype AA sequence MFCGRLNMHM NVQNGKWDSD PSGTKTCIDT KEGILQYCQE VYPELQITNV VEANQPVTIQ
NWCKRGRKQC KTHPHFVIPY RCLVGEFVSD ALLVPDKCKF LHQERMDVCE THLHWHTVAK
ETCSEKSTNL HDYGMLLPCG IDKFRGVEFV CCPLAEESDN VDSADAEEDD SDVWWGGADT
DYADGSEDKV VEVAEEEEVA EVEEEEADDD EDDEDGDEVE EEAEEPYEEA TERTTSIATT
TTTTTESVEE VVRVPTTAAS TPDAVDKYLE TPGDENEHAH FQKAKERLEA KHRERMSQVM
REWEEAERQA KNLPKADKKA VIQHFQEKVE SLEQEAANER QQLVETHMAR VEAMLNDRRR
LALENYITAL QAVPPRPRHV FNMLKKYVRA EQKDRQHTLK HFEHVRMVDP KKAAQIRSQV
MTHLRVIYER MNQSLSLLYN VPAVAEEIQD EVDELLQKEQ NYSDDVLANM ISEPRISYGN
DALMPSLTET KTTVELLPVN GEFSLDDLQP WHSFGADSVP ANTENEVEPV DARPAADRGL
TTRPGSGLTN IKTEEISEVK MDAEFRHDSG YEVHHQKLVF FAEDVGSNKG AIIGLMVGGV
VIATVIVITL VMLKKKQYTS IHHGVVEVDA AVTPEERHLS KMQQNGYENP TYKFFEQMQN
*
mutated AA sequence MFCGRLNMHM NVQNGKWDSD PSGTKTCIDT KEGILQYCQE VYPELQITNV VEANQPVTIQ
NWCKRGRKQC KTHPHFVIPY RCLVGEFVSD ALLVPDKCKF LHQERMDVCE THLHWHTVAK
ETCSEKSTNL HDYGMLLPCG IDKFRGVEFV CCPLAEESDN VDSADAEEDD SDVWWGGADT
DYADGSEDKV VEVAEEEEVA EVEEEEADDD EDDEDGDEVE EEAEEPYEEA TERTTSIATT
TTTTTESVEE VVRVPTTAAS TPDAVDKYLE TPGDENEHAH FQKAKERLEA KHRERMSQVM
REWEEAERQA KNLPKADKKA VIQHFQEKVE SLEQEAANER QQLVETHMAR VEAMLNDRRR
LALENYITAL QAVPPRPRHV FNMLKKYVRA EQKDRQHTLK HFEHVRMVDP KKAAQIRSQV
MTHLRVIYER MNQSLSLLYN VPAVAEEIQD EVDELLQKEQ NYSDDVLANM ISEPRISYGN
DALMPSLTET KTTVELLPVN GEFSLDDLQP WHSFGADSVP ANTENEVEPV DARPAADRGL
TTRPGSGLTN IKTEEISEVK MDAEFRHDSG YEVHHQKLVF FGEDVGSNKG AIIGLMVGGV
VIATVIVITL VMLKKKQYTS IHHGVVEVDA AVTPEERHLS KMQQNGYENP TYKFFEQMQN
*
speed 0.92 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
back to results table
Yum, tasty mutations...

mutation t@sting

 documentation

Prediction

disease causing

 Model: simple_aae, prob: 0.999999798195631 (classification due to ClinVar, real probability is shown anyway)      (explain)
Summary
  • amino acid sequence changed
  • known disease mutation at this position (HGMD CM920065)
  • known disease mutation: rs18091 (pathogenic)
  • protein features (might be) affected
  • splice site changes
 hyperlink
analysed issue analysis result
name of alteration no title
alteration (phys. location) chr21:27264170G>CN/A show variant in all transcripts   IGV
HGNC symbol APP
Ensembl transcript ID ENST00000346798
Genbank transcript ID NM_000484
UniProt peptide P05067
alteration type single base exchange
alteration region CDS
DNA changes c.2075C>G
cDNA.2109C>G
g.279277C>G
AA changes A692G Score: 60 explain score(s)
position(s) of altered AA
if AA alteration in CDS		 692
frameshift no
known variant Reference ID: rs63750671
Allele 'C' was neither found in ExAC nor 1000G.
known disease mutation: rs18091 (pathogenic for Alzheimer disease|Alzheimer disease, type 1|ABetaA21G amyloidosis|not provided) dbSNP  NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM920065)

known disease mutation at this position, please check HGMD for details (HGMD ID CM920065)
known disease mutation at this position, please check HGMD for details (HGMD ID CM920065)
regulatory features H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
phyloP / phastCons
PhyloPPhastCons
(flanking)-2.20.042
4.0560.998
(flanking)2.9711
explain score(s) and/or inspect your position(s) in in UCSC Genome Browser
splice sites
effectgDNA positionscorewt detection sequence exon-intron border
Acc marginally increased279267wt: 0.3597 / mu: 0.3618 (marginal change - not scored)wt: TTTCTTAATTTGTTTTCAAGGTGTTCTTTGCAGAAGATGTG
mu: TTTCTTAATTTGTTTTCAAGGTGTTCTTTGGAGAAGATGTG		 aagg|TGTT
Donor marginally increased279276wt: 0.9493 / mu: 0.9953 (marginal change - not scored)wt: TCTTTGCAGAAGATG
mu: TCTTTGGAGAAGATG		 TTTG|caga
Donor marginally increased279279wt: 0.6197 / mu: 0.6710 (marginal change - not scored)wt: TTGCAGAAGATGTGG
mu: TTGGAGAAGATGTGG		 GCAG|aaga
Acc gained2792760.35mu: TTGTTTTCAAGGTGTTCTTTGGAGAAGATGTGGGTTCAAAC tttg|GAGA
Donor gained2792730.53mu: TGTTCTTTGGAGAAG TTCT|ttgg
distance from splice site 11
Kozak consensus sequence altered? N/A
conservation
protein level for non-synonymous changes
speciesmatchgeneaaalignment
Human      692YEVHHQKLVFFAEDVGSNKGAIIG
mutated  not conserved    692YEVHHQKLVFFGEDVGSNKGAII
Ptroglodytes  all identical  ENSPTRG00000013811  692YEVHHQKLVFFAEDVGSNKGAII
Mmulatta  all identical  ENSMMUG00000014384  692YEVHHQKLVFFAEDVGSNKGAII
Fcatus  all identical  ENSFCAG00000001556  673YEVHHQKLVFFAEDVGSNKGAII
Mmusculus  all identical  ENSMUSG00000022892  617FEVRHQKLVFFAEDVGSNKGAII
Ggallus  all identical  ENSGALG00000015770  673YEVHHQKLVFFAEDVGSNKGAII
Trubripes  all identical  ENSTRUG00000010470  686YEVHHQKLVFFAEDVGSNKGAII
Drerio  all identical  ENSDARG00000055543  683YDVRDKRLMFLAEDMGSNKGAII
Dmelanogaster  no alignment  FBgn0000108  n/a
Celegans  not conserved  C42D8.8  609ASFYRHDKLIQSPEVERSASSVFQ
Xtropicalis  all identical  ENSXETG00000013612  693YEVHHQKLVFFAEEVGSNKGAII
protein features
start (aa)end (aa)featuredetails 
18699TOPO_DOMExtracellular (Potential).lost
688691STRANDmight get lost (downstream of altered splice site)
688711PEPTIDEP3(40). /FTId=PRO_0000000096.lost
688713PEPTIDEP3(42). /FTId=PRO_0000000095.lost
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)
704704SITEImplicated in free radical propagation (By similarity).might get lost (downstream of altered splice site)
704704MUTAGENG->V: Reduced protein oxidation. 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)
706706MUTAGENM->V: No free radical production. No hippocampal neuron toxicity.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->C,S: Unchanged beta-APP42/total APP- beta 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)
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)
743743MOD_RESPhosphothreonine; by CDK5 and MAPK10.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)
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)
757757CONFLICTY -> S (in Ref. 30; AAA35540).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)
757757MUTAGENY->G: Loss of binding to MAPK8IP1, APBA1, APBB1, APPBP2 and SHC1.might get lost (downstream of altered splice site)
757757MOD_RESPhosphotyrosine; by ABL1 (By similarity).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)
762762MOD_RESPhosphotyrosine.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)
763765STRANDmight get lost (downstream of altered splice site)
length of protein normal
AA sequence altered yes
position of stopcodon in wt / mu CDS 2313 / 2313
position (AA) of stopcodon in wt / mu AA sequence 771 / 771
position of stopcodon in wt / mu cDNA 2347 / 2347
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 2246
theoretical NMD boundary in CDS 2161
length of CDS 2313
coding sequence (CDS) position 2075
cDNA position
(for ins/del: last normal base / first normal base)		 2109
gDNA position
(for ins/del: last normal base / first normal base)		 279277
chromosomal position
(for ins/del: last normal base / first normal base)		 27264170
original gDNA sequence snippet TGTTTTCAAGGTGTTCTTTGCAGAAGATGTGGGTTCAAACA
altered gDNA sequence snippet TGTTTTCAAGGTGTTCTTTGGAGAAGATGTGGGTTCAAACA
original cDNA sequence snippet TCAAAAATTGGTGTTCTTTGCAGAAGATGTGGGTTCAAACA
altered cDNA sequence snippet TCAAAAATTGGTGTTCTTTGGAGAAGATGTGGGTTCAAACA
wildtype AA sequence MLPGLALLLL AAWTARALEV PTDGNAGLLA EPQIAMFCGR LNMHMNVQNG KWDSDPSGTK
TCIDTKEGIL QYCQEVYPEL QITNVVEANQ PVTIQNWCKR GRKQCKTHPH FVIPYRCLVG
EFVSDALLVP DKCKFLHQER MDVCETHLHW HTVAKETCSE KSTNLHDYGM LLPCGIDKFR
GVEFVCCPLA EESDNVDSAD AEEDDSDVWW GGADTDYADG SEDKVVEVAE EEEVAEVEEE
EADDDEDDED GDEVEEEAEE PYEEATERTT SIATTTTTTT ESVEEVVREV CSEQAETGPC
RAMISRWYFD VTEGKCAPFF YGGCGGNRNN FDTEEYCMAV CGSAMSQSLL KTTQEPLARD
PVKLPTTAAS TPDAVDKYLE TPGDENEHAH FQKAKERLEA KHRERMSQVM REWEEAERQA
KNLPKADKKA VIQHFQEKVE SLEQEAANER QQLVETHMAR VEAMLNDRRR LALENYITAL
QAVPPRPRHV FNMLKKYVRA EQKDRQHTLK HFEHVRMVDP KKAAQIRSQV MTHLRVIYER
MNQSLSLLYN VPAVAEEIQD EVDELLQKEQ NYSDDVLANM ISEPRISYGN DALMPSLTET
KTTVELLPVN GEFSLDDLQP WHSFGADSVP ANTENEVEPV DARPAADRGL TTRPGSGLTN
IKTEEISEVK MDAEFRHDSG YEVHHQKLVF FAEDVGSNKG AIIGLMVGGV VIATVIVITL
VMLKKKQYTS IHHGVVEVDA AVTPEERHLS KMQQNGYENP TYKFFEQMQN *
mutated AA sequence MLPGLALLLL AAWTARALEV PTDGNAGLLA EPQIAMFCGR LNMHMNVQNG KWDSDPSGTK
TCIDTKEGIL QYCQEVYPEL QITNVVEANQ PVTIQNWCKR GRKQCKTHPH FVIPYRCLVG
EFVSDALLVP DKCKFLHQER MDVCETHLHW HTVAKETCSE KSTNLHDYGM LLPCGIDKFR
GVEFVCCPLA EESDNVDSAD AEEDDSDVWW GGADTDYADG SEDKVVEVAE EEEVAEVEEE
EADDDEDDED GDEVEEEAEE PYEEATERTT SIATTTTTTT ESVEEVVREV CSEQAETGPC
RAMISRWYFD VTEGKCAPFF YGGCGGNRNN FDTEEYCMAV CGSAMSQSLL KTTQEPLARD
PVKLPTTAAS TPDAVDKYLE TPGDENEHAH FQKAKERLEA KHRERMSQVM REWEEAERQA
KNLPKADKKA VIQHFQEKVE SLEQEAANER QQLVETHMAR VEAMLNDRRR LALENYITAL
QAVPPRPRHV FNMLKKYVRA EQKDRQHTLK HFEHVRMVDP KKAAQIRSQV MTHLRVIYER
MNQSLSLLYN VPAVAEEIQD EVDELLQKEQ NYSDDVLANM ISEPRISYGN DALMPSLTET
KTTVELLPVN GEFSLDDLQP WHSFGADSVP ANTENEVEPV DARPAADRGL TTRPGSGLTN
IKTEEISEVK MDAEFRHDSG YEVHHQKLVF FGEDVGSNKG AIIGLMVGGV VIATVIVITL
VMLKKKQYTS IHHGVVEVDA AVTPEERHLS KMQQNGYENP TYKFFEQMQN *
speed 0.37 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
back to results table
Yum, tasty mutations...

mutation t@sting

 documentation

Prediction

disease causing

 Model: simple_aae, prob: 0.999999936808366 (classification due to ClinVar, real probability is shown anyway)      (explain)
Summary
  • amino acid sequence changed
  • known disease mutation at this position (HGMD CM920065)
  • known disease mutation: rs18091 (pathogenic)
  • protein features (might be) affected
  • splice site changes
 hyperlink
analysed issue analysis result
name of alteration no title
alteration (phys. location) chr21:27264170G>CN/A show variant in all transcripts   IGV
HGNC symbol APP
Ensembl transcript ID ENST00000358918
Genbank transcript ID NM_001204301
UniProt peptide P05067
alteration type single base exchange
alteration region CDS
DNA changes c.2021C>G
cDNA.2221C>G
g.279277C>G
AA changes A674G Score: 60 explain score(s)
position(s) of altered AA
if AA alteration in CDS		 674
frameshift no
known variant Reference ID: rs63750671
Allele 'C' was neither found in ExAC nor 1000G.
known disease mutation: rs18091 (pathogenic for Alzheimer disease|Alzheimer disease, type 1|ABetaA21G amyloidosis|not provided) dbSNP  NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM920065)

known disease mutation at this position, please check HGMD for details (HGMD ID CM920065)
known disease mutation at this position, please check HGMD for details (HGMD ID CM920065)
regulatory features H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
phyloP / phastCons
PhyloPPhastCons
(flanking)-2.20.042
4.0560.998
(flanking)2.9711
explain score(s) and/or inspect your position(s) in in UCSC Genome Browser
splice sites
effectgDNA positionscorewt detection sequence exon-intron border
Acc marginally increased279267wt: 0.3597 / mu: 0.3618 (marginal change - not scored)wt: TTTCTTAATTTGTTTTCAAGGTGTTCTTTGCAGAAGATGTG
mu: TTTCTTAATTTGTTTTCAAGGTGTTCTTTGGAGAAGATGTG		 aagg|TGTT
Donor marginally increased279276wt: 0.9493 / mu: 0.9953 (marginal change - not scored)wt: TCTTTGCAGAAGATG
mu: TCTTTGGAGAAGATG		 TTTG|caga
Donor marginally increased279279wt: 0.6197 / mu: 0.6710 (marginal change - not scored)wt: TTGCAGAAGATGTGG
mu: TTGGAGAAGATGTGG		 GCAG|aaga
Acc gained2792760.35mu: TTGTTTTCAAGGTGTTCTTTGGAGAAGATGTGGGTTCAAAC tttg|GAGA
Donor gained2792730.53mu: TGTTCTTTGGAGAAG TTCT|ttgg
distance from splice site 11
Kozak consensus sequence altered? N/A
conservation
protein level for non-synonymous changes
speciesmatchgeneaaalignment
Human      674YEVHHQKLVFFAEDVGSNKGAIIG
mutated  not conserved    674YEVHHQKLVFFGEDVGSNKGAII
Ptroglodytes  all identical  ENSPTRG00000013811  692YEVHHQKLVFFAEDVGSNKGAII
Mmulatta  all identical  ENSMMUG00000014384  692YEVHHQKLVFFAEDVGSNKGAII
Fcatus  all identical  ENSFCAG00000001556  673YEVHHQKLVFFAEDVGSNKGAII
Mmusculus  all identical  ENSMUSG00000022892  617FEVRHQKLVFFAEDVGSNKGAII
Ggallus  all identical  ENSGALG00000015770  673YEVHHQKLVFFAEDVGSNKGAII
Trubripes  all identical  ENSTRUG00000010470  686YEVHHQKLVFFAEDVGSNKGAII
Drerio  all identical  ENSDARG00000055543  672YDVRDKRLMFLAEDMGSNKGAII
Dmelanogaster  no alignment  FBgn0000108  n/a
Celegans  not conserved  C42D8.8  609ASFYRHDKLIQSPEVERSASSVFQ
Xtropicalis  all identical  ENSXETG00000013612  693YEVHHQKLVFFAEEVGSNKGAII
protein features
start (aa)end (aa)featuredetails 
18699TOPO_DOMExtracellular (Potential).lost
672673SITECleavage; by caspase-6; when associated with variant 670-N-L-671.might get lost (downstream of altered splice site)
674677TURNlost
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)
706706SITESusceptible to oxidation.might get lost (downstream of altered splice site)
706706MUTAGENM->L: Reduced lipid peroxidation inhibition.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->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->K: Decreased beta-APP42/total APP-beta ratio.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->A: No cleavage by caspases during apoptosis.might get lost (downstream of altered splice site)
739739MUTAGEND->N: No effect on FADD-induced 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)
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)
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)
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)
762762MOD_RESPhosphotyrosine.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)
763765STRANDmight get lost (downstream of altered splice site)
length of protein normal
AA sequence altered yes
position of stopcodon in wt / mu CDS 2259 / 2259
position (AA) of stopcodon in wt / mu AA sequence 753 / 753
position of stopcodon in wt / mu cDNA 2459 / 2459
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 201 / 201
chromosome 21
strand -1
last intron/exon boundary 2358
theoretical NMD boundary in CDS 2107
length of CDS 2259
coding sequence (CDS) position 2021
cDNA position
(for ins/del: last normal base / first normal base)		 2221
gDNA position
(for ins/del: last normal base / first normal base)		 279277
chromosomal position
(for ins/del: last normal base / first normal base)		 27264170
original gDNA sequence snippet TGTTTTCAAGGTGTTCTTTGCAGAAGATGTGGGTTCAAACA
altered gDNA sequence snippet TGTTTTCAAGGTGTTCTTTGGAGAAGATGTGGGTTCAAACA
original cDNA sequence snippet TCAAAAATTGGTGTTCTTTGCAGAAGATGTGGGTTCAAACA
altered cDNA sequence snippet TCAAAAATTGGTGTTCTTTGGAGAAGATGTGGGTTCAAACA
wildtype AA sequence MLPGLALLLL AAWTARALEV PTDGNAGLLA EPQIAMFCGR LNMHMNVQNG KWDSDPSGTK
TCIDTKEGIL QYCQEVYPEL QITNVVEANQ PVTIQNWCKR GRKQCKTHPH FVIPYRCLVG
EFVSDALLVP DKCKFLHQER MDVCETHLHW HTVAKETCSE KSTNLHDYGM LLPCGIDKFR
GVEFVCCPLA EESDNVDSAD AEEDDSDVWW GGADTDYADG SEDKVVEVAE EEEVAEVEEE
EADDDEDDED GDEVEEEAEE PYEEATERTT SIATTTTTTT ESVEEVVREV CSEQAETGPC
RAMISRWYFD VTEGKCAPFF YGGCGGNRNN FDTEEYCMAV CGSAMSQSLL KTTQEPLARD
PVKLPTTAAS TPDAVDKYLE TPGDENEHAH FQKAKERLEA KHRERMSQVM REWEEAERQA
KNLPKADKKA VIQHFQEKVE SLEQEAANER QQLVETHMAR VEAMLNDRRR LALENYITAL
QAVPPRPRHV FNMLKKYVRA EQKDRQHTLK HFEHVRMVDP KKAAQIRSQV MTHLRVIYER
MNQSLSLLYN VPAVAEEIQD EVDELLQKEQ NYSDDVLANM ISEPRISYGN DALMPSLTET
KTTVELLPVN GEFSLDDLQP WHSFGADSVP ANTENEGSGL TNIKTEEISE VKMDAEFRHD
SGYEVHHQKL VFFAEDVGSN KGAIIGLMVG GVVIATVIVI TLVMLKKKQY TSIHHGVVEV
DAAVTPEERH LSKMQQNGYE NPTYKFFEQM QN*
mutated AA sequence MLPGLALLLL AAWTARALEV PTDGNAGLLA EPQIAMFCGR LNMHMNVQNG KWDSDPSGTK
TCIDTKEGIL QYCQEVYPEL QITNVVEANQ PVTIQNWCKR GRKQCKTHPH FVIPYRCLVG
EFVSDALLVP DKCKFLHQER MDVCETHLHW HTVAKETCSE KSTNLHDYGM LLPCGIDKFR
GVEFVCCPLA EESDNVDSAD AEEDDSDVWW GGADTDYADG SEDKVVEVAE EEEVAEVEEE
EADDDEDDED GDEVEEEAEE PYEEATERTT SIATTTTTTT ESVEEVVREV CSEQAETGPC
RAMISRWYFD VTEGKCAPFF YGGCGGNRNN FDTEEYCMAV CGSAMSQSLL KTTQEPLARD
PVKLPTTAAS TPDAVDKYLE TPGDENEHAH FQKAKERLEA KHRERMSQVM REWEEAERQA
KNLPKADKKA VIQHFQEKVE SLEQEAANER QQLVETHMAR VEAMLNDRRR LALENYITAL
QAVPPRPRHV FNMLKKYVRA EQKDRQHTLK HFEHVRMVDP KKAAQIRSQV MTHLRVIYER
MNQSLSLLYN VPAVAEEIQD EVDELLQKEQ NYSDDVLANM ISEPRISYGN DALMPSLTET
KTTVELLPVN GEFSLDDLQP WHSFGADSVP ANTENEGSGL TNIKTEEISE VKMDAEFRHD
SGYEVHHQKL VFFGEDVGSN KGAIIGLMVG GVVIATVIVI TLVMLKKKQY TSIHHGVVEV
DAAVTPEERH LSKMQQNGYE NPTYKFFEQM QN*
speed 0.86 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
back to results table
Yum, tasty mutations...

mutation t@sting

 documentation

Prediction

disease causing

 Model: simple_aae, prob: 0.999999947590514 (classification due to ClinVar, real probability is shown anyway)      (explain)
Summary
  • amino acid sequence changed
  • known disease mutation at this position (HGMD CM920065)
  • known disease mutation: rs18091 (pathogenic)
  • protein features (might be) affected
  • splice site changes
 hyperlink
analysed issue analysis result
name of alteration no title
alteration (phys. location) chr21:27264170G>CN/A show variant in all transcripts   IGV
HGNC symbol APP
Ensembl transcript ID ENST00000354192
Genbank transcript ID NM_001136129
UniProt peptide P05067
alteration type single base exchange
alteration region CDS
DNA changes c.1682C>G
cDNA.1809C>G
g.279277C>G
AA changes A561G Score: 60 explain score(s)
position(s) of altered AA
if AA alteration in CDS		 561
frameshift no
known variant Reference ID: rs63750671
Allele 'C' was neither found in ExAC nor 1000G.
known disease mutation: rs18091 (pathogenic for Alzheimer disease|Alzheimer disease, type 1|ABetaA21G amyloidosis|not provided) dbSNP  NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM920065)

known disease mutation at this position, please check HGMD for details (HGMD ID CM920065)
known disease mutation at this position, please check HGMD for details (HGMD ID CM920065)
regulatory features H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
phyloP / phastCons
PhyloPPhastCons
(flanking)-2.20.042
4.0560.998
(flanking)2.9711
explain score(s) and/or inspect your position(s) in in UCSC Genome Browser
splice sites
effectgDNA positionscorewt detection sequence exon-intron border
Acc marginally increased279267wt: 0.3597 / mu: 0.3618 (marginal change - not scored)wt: TTTCTTAATTTGTTTTCAAGGTGTTCTTTGCAGAAGATGTG
mu: TTTCTTAATTTGTTTTCAAGGTGTTCTTTGGAGAAGATGTG		 aagg|TGTT
Donor marginally increased279276wt: 0.9493 / mu: 0.9953 (marginal change - not scored)wt: TCTTTGCAGAAGATG
mu: TCTTTGGAGAAGATG		 TTTG|caga
Donor marginally increased279279wt: 0.6197 / mu: 0.6710 (marginal change - not scored)wt: TTGCAGAAGATGTGG
mu: TTGGAGAAGATGTGG		 GCAG|aaga
Acc gained2792760.35mu: TTGTTTTCAAGGTGTTCTTTGGAGAAGATGTGGGTTCAAAC tttg|GAGA
Donor gained2792730.53mu: TGTTCTTTGGAGAAG TTCT|ttgg
distance from splice site 11
Kozak consensus sequence altered? N/A
conservation
protein level for non-synonymous changes
speciesmatchgeneaaalignment
Human      561YEVHHQKLVFFAEDVGSNKGAIIG
mutated  not conserved    561YEVHHQKLVFFGEDVGSNKGAII
Ptroglodytes  all identical  ENSPTRG00000013811  692YEVHHQKLVFFAEDVGSNKGAII
Mmulatta  all identical  ENSMMUG00000014384  692YEVHHQKLVFFAEDVGSNKGAII
Fcatus  all identical  ENSFCAG00000001556  673YEVHHQKLVFFAEDVGSNKGAII
Mmusculus  all identical  ENSMUSG00000022892  617FFAEDVGSNKGAII
Ggallus  all identical  ENSGALG00000015770  673AEDVGSNKGAII
Trubripes  all identical  ENSTRUG00000010470  686YEVHHQKLVFFAEDVGSNKGAII
Drerio  all identical  ENSDARG00000055543  673YDVRDKRLMFLAEDMGSNKGAII
Dmelanogaster  no alignment  FBgn0000108  n/a
Celegans  not conserved  C42D8.8  610SPEVERSASSVFQ
Xtropicalis  all identical  ENSXETG00000013612  693YEVHHQKLVFFAEEVGSNKGAII
protein features
start (aa)end (aa)featuredetails 
18699TOPO_DOMExtracellular (Potential).lost
552566HELIXlost
571571CARBOHYDN-linked (GlcNAc...) (Probable).might get lost (downstream of altered splice site)
614614CARBOHYDO-linked (GalNAc...).might get lost (downstream of altered splice site)
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)
656656CARBOHYDO-linked (Xyl...) (chondroitin sulfate); in L-APP isoforms.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)
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)
684684MUTAGENH->R: Only 23% zinc-induced beta-APP (28) peptide aggregation.might get lost (downstream of altered splice site)
684684METALCopper or zinc 2.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)
704704SITEImplicated in free radical propagation (By similarity).might get lost (downstream of altered splice site)
704704MUTAGENG->V: Reduced protein oxidation. No hippocampal neuron toxicity.might get lost (downstream of altered splice site)
706706SITESusceptible to oxidation.might get lost (downstream of altered splice site)
706706MUTAGENM->L: Reduced lipid peroxidation inhibition.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)
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->F,G,I: Increased beta-APP42/beta-APP40 ratio.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)
717717MUTAGENV->K: Decreased beta-APP42/total APP-beta 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)
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)
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)
743743MUTAGENT->E: Reduced NGF-stimulated neurite extension. No effect on APP maturation.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->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)
757757MOD_RESPhosphotyrosine; by ABL1 (By similarity).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)
757757CONFLICTY -> S (in Ref. 30; AAA35540).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)
762762MOD_RESPhosphotyrosine.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)
763765STRANDmight get lost (downstream of altered splice site)
length of protein normal
AA sequence altered yes
position of stopcodon in wt / mu CDS 1920 / 1920
position (AA) of stopcodon in wt / mu AA sequence 640 / 640
position of stopcodon in wt / mu cDNA 2047 / 2047
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 128 / 128
chromosome 21
strand -1
last intron/exon boundary 1946
theoretical NMD boundary in CDS 1768
length of CDS 1920
coding sequence (CDS) position 1682
cDNA position
(for ins/del: last normal base / first normal base)		 1809
gDNA position
(for ins/del: last normal base / first normal base)		 279277
chromosomal position
(for ins/del: last normal base / first normal base)		 27264170
original gDNA sequence snippet TGTTTTCAAGGTGTTCTTTGCAGAAGATGTGGGTTCAAACA
altered gDNA sequence snippet TGTTTTCAAGGTGTTCTTTGGAGAAGATGTGGGTTCAAACA
original cDNA sequence snippet TCAAAAATTGGTGTTCTTTGCAGAAGATGTGGGTTCAAACA
altered cDNA sequence snippet TCAAAAATTGGTGTTCTTTGGAGAAGATGTGGGTTCAAACA
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 VRVPTTAAST
PDAVDKYLET PGDENEHAHF QKAKERLEAK HRERMSQVMR EWEEAERQAK NLPKADKKAV
IQHFQEKVES LEQEAANERQ QLVETHMARV EAMLNDRRRL ALENYITALQ AVPPRPRHVF
NMLKKYVRAE QKDRQHTLKH FEHVRMVDPK KAAQIRSQVM THLRVIYERM NQSLSLLYNV
PAVAEEIQDE VDELLQKEQN YSDDVLANMI SEPRISYGND ALMPSLTETK TTVELLPVNG
EFSLDDLQPW HSFGADSVPA NTENEVEPVD ARPAADRGLT TRPGSGLTNI KTEEISEVKM
DAEFRHDSGY EVHHQKLVFF AEDVGSNKGA IIGLMVGGVV IATVIVITLV MLKKKQYTSI
HHGVVEVDAA VTPEERHLSK MQQNGYENPT YKFFEQMQN*
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 VRVPTTAAST
PDAVDKYLET PGDENEHAHF QKAKERLEAK HRERMSQVMR EWEEAERQAK NLPKADKKAV
IQHFQEKVES LEQEAANERQ QLVETHMARV EAMLNDRRRL ALENYITALQ AVPPRPRHVF
NMLKKYVRAE QKDRQHTLKH FEHVRMVDPK KAAQIRSQVM THLRVIYERM NQSLSLLYNV
PAVAEEIQDE VDELLQKEQN YSDDVLANMI SEPRISYGND ALMPSLTETK TTVELLPVNG
EFSLDDLQPW HSFGADSVPA NTENEVEPVD ARPAADRGLT TRPGSGLTNI KTEEISEVKM
DAEFRHDSGY EVHHQKLVFF GEDVGSNKGA IIGLMVGGVV IATVIVITLV MLKKKQYTSI
HHGVVEVDAA VTPEERHLSK MQQNGYENPT YKFFEQMQN*
speed 0.86 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
back to results table
Yum, tasty mutations...

mutation t@sting

 documentation

Prediction

disease causing

 Model: simple_aae, prob: 0.99999999992583 (classification due to ClinVar, real probability is shown anyway)      (explain)
Summary
  • amino acid sequence changed
  • known disease mutation at this position (HGMD CM920065)
  • known disease mutation: rs18091 (pathogenic)
  • protein features (might be) affected
  • splice site changes
 hyperlink
analysed issue analysis result
name of alteration no title
alteration (phys. location) chr21:27264170G>CN/A show variant in all transcripts   IGV
HGNC symbol APP
Ensembl transcript ID ENST00000357903
Genbank transcript ID NM_201413
UniProt peptide P05067
alteration type single base exchange
alteration region CDS
DNA changes c.2018C>G
cDNA.2185C>G
g.279277C>G
AA changes A673G Score: 60 explain score(s)
position(s) of altered AA
if AA alteration in CDS		 673
frameshift no
known variant Reference ID: rs63750671
Allele 'C' was neither found in ExAC nor 1000G.
known disease mutation: rs18091 (pathogenic for Alzheimer disease|Alzheimer disease, type 1|ABetaA21G amyloidosis|not provided) dbSNP  NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM920065)

known disease mutation at this position, please check HGMD for details (HGMD ID CM920065)
known disease mutation at this position, please check HGMD for details (HGMD ID CM920065)
regulatory features H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
phyloP / phastCons
PhyloPPhastCons
(flanking)-2.20.042
4.0560.998
(flanking)2.9711
explain score(s) and/or inspect your position(s) in in UCSC Genome Browser
splice sites
effectgDNA positionscorewt detection sequence exon-intron border
Acc marginally increased279267wt: 0.3597 / mu: 0.3618 (marginal change - not scored)wt: TTTCTTAATTTGTTTTCAAGGTGTTCTTTGCAGAAGATGTG
mu: TTTCTTAATTTGTTTTCAAGGTGTTCTTTGGAGAAGATGTG		 aagg|TGTT
Donor marginally increased279276wt: 0.9493 / mu: 0.9953 (marginal change - not scored)wt: TCTTTGCAGAAGATG
mu: TCTTTGGAGAAGATG		 TTTG|caga
Donor marginally increased279279wt: 0.6197 / mu: 0.6710 (marginal change - not scored)wt: TTGCAGAAGATGTGG
mu: TTGGAGAAGATGTGG		 GCAG|aaga
Acc gained2792760.35mu: TTGTTTTCAAGGTGTTCTTTGGAGAAGATGTGGGTTCAAAC tttg|GAGA
Donor gained2792730.53mu: TGTTCTTTGGAGAAG TTCT|ttgg
distance from splice site 11
Kozak consensus sequence altered? N/A
conservation
protein level for non-synonymous changes
speciesmatchgeneaaalignment
Human      673YEVHHQKLVFFAEDVGSNKGAIIG
mutated  not conserved    673YEVHHQKLVFFGEDVGSNKGAII
Ptroglodytes  all identical  ENSPTRG00000013811  692YEVHHQKLVFFAEDVGSNKGAII
Mmulatta  all identical  ENSMMUG00000014384  692YEVHHQKLVFFAEDVGSNKGAII
Fcatus  all identical  ENSFCAG00000001556  673YEVHHQKLVFFAEDVGSNKGAII
Mmusculus  all identical  ENSMUSG00000022892  617FEVRHQKLVFFAEDVGSNKGAII
Ggallus  all identical  ENSGALG00000015770  673YEVHHQKLVFFAEDVGSNKGAII
Trubripes  all identical  ENSTRUG00000010470  686YEVHHQKLVFFAEDVGSNKGAII
Drerio  all identical  ENSDARG00000055543  673YDVRDKRLMFLAEDMGSNKGAII
Dmelanogaster  no alignment  FBgn0000108  n/a
Celegans  not conserved  C42D8.8  618ASFYRHDKLIQSPEVER
Xtropicalis  all identical  ENSXETG00000013612  693YEVHHQKLVFFAEEVGSNKGAII
protein features
start (aa)end (aa)featuredetails 
18699TOPO_DOMExtracellular (Potential).lost
671672SITECleavage; by beta-secretase.might get lost (downstream of altered splice site)
672673SITECleavage; by caspase-6; when associated with variant 670-N-L-671.lost
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)
684684MUTAGENH->R: Only 23% zinc-induced beta-APP (28) peptide aggregation.might get lost (downstream of altered splice site)
684684METALCopper or zinc 2.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)
704704SITEImplicated in free radical propagation (By similarity).might get lost (downstream of altered splice site)
704704MUTAGENG->V: Reduced protein oxidation. No hippocampal neuron toxicity.might get lost (downstream of altered splice site)
706706SITESusceptible to oxidation.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)
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->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)
717717MUTAGENV->F,G,I: Increased beta-APP42/beta-APP40 ratio.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)
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->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)
743743MOD_RESPhosphothreonine; by CDK5 and MAPK10.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)
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)
757757CONFLICTY -> S (in Ref. 30; AAA35540).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)
757757MUTAGENY->G: Loss of binding to MAPK8IP1, APBA1, APBB1, APPBP2 and SHC1.might get lost (downstream of altered splice site)
757757MOD_RESPhosphotyrosine; by ABL1 (By similarity).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)
762762MOD_RESPhosphotyrosine.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)
763765STRANDmight get lost (downstream of altered splice site)
length of protein normal
AA sequence altered yes
position of stopcodon in wt / mu CDS 2256 / 2256
position (AA) of stopcodon in wt / mu AA sequence 752 / 752
position of stopcodon in wt / mu cDNA 2423 / 2423
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 168 / 168
chromosome 21
strand -1
last intron/exon boundary 2322
theoretical NMD boundary in CDS 2104
length of CDS 2256
coding sequence (CDS) position 2018
cDNA position
(for ins/del: last normal base / first normal base)		 2185
gDNA position
(for ins/del: last normal base / first normal base)		 279277
chromosomal position
(for ins/del: last normal base / first normal base)		 27264170
original gDNA sequence snippet TGTTTTCAAGGTGTTCTTTGCAGAAGATGTGGGTTCAAACA
altered gDNA sequence snippet TGTTTTCAAGGTGTTCTTTGGAGAAGATGTGGGTTCAAACA
original cDNA sequence snippet TCAAAAATTGGTGTTCTTTGCAGAAGATGTGGGTTCAAACA
altered cDNA sequence snippet TCAAAAATTGGTGTTCTTTGGAGAAGATGTGGGTTCAAACA
wildtype AA sequence MLPGLALLLL AAWTARALEV PTDGNAGLLA EPQIAMFCGR LNMHMNVQNG KWDSDPSGTK
TCIDTKEGIL QYCQEVYPEL QITNVVEANQ PVTIQNWCKR GRKQCKTHPH FVIPYRCLVG
EFVSDALLVP DKCKFLHQER MDVCETHLHW HTVAKETCSE KSTNLHDYGM LLPCGIDKFR
GVEFVCCPLA EESDNVDSAD AEEDDSDVWW GGADTDYADG SEDKVVEVAE EEEVAEVEEE
EADDDEDDED GDEVEEEAEE PYEEATERTT SIATTTTTTT ESVEEVVREV CSEQAETGPC
RAMISRWYFD VTEGKCAPFF YGGCGGNRNN FDTEEYCMAV CGSAIPTTAA STPDAVDKYL
ETPGDENEHA HFQKAKERLE AKHRERMSQV MREWEEAERQ AKNLPKADKK AVIQHFQEKV
ESLEQEAANE RQQLVETHMA RVEAMLNDRR RLALENYITA LQAVPPRPRH VFNMLKKYVR
AEQKDRQHTL KHFEHVRMVD PKKAAQIRSQ VMTHLRVIYE RMNQSLSLLY NVPAVAEEIQ
DEVDELLQKE QNYSDDVLAN MISEPRISYG NDALMPSLTE TKTTVELLPV NGEFSLDDLQ
PWHSFGADSV PANTENEVEP VDARPAADRG LTTRPGSGLT NIKTEEISEV KMDAEFRHDS
GYEVHHQKLV FFAEDVGSNK GAIIGLMVGG VVIATVIVIT LVMLKKKQYT SIHHGVVEVD
AAVTPEERHL SKMQQNGYEN PTYKFFEQMQ N*
mutated AA sequence MLPGLALLLL AAWTARALEV PTDGNAGLLA EPQIAMFCGR LNMHMNVQNG KWDSDPSGTK
TCIDTKEGIL QYCQEVYPEL QITNVVEANQ PVTIQNWCKR GRKQCKTHPH FVIPYRCLVG
EFVSDALLVP DKCKFLHQER MDVCETHLHW HTVAKETCSE KSTNLHDYGM LLPCGIDKFR
GVEFVCCPLA EESDNVDSAD AEEDDSDVWW GGADTDYADG SEDKVVEVAE EEEVAEVEEE
EADDDEDDED GDEVEEEAEE PYEEATERTT SIATTTTTTT ESVEEVVREV CSEQAETGPC
RAMISRWYFD VTEGKCAPFF YGGCGGNRNN FDTEEYCMAV CGSAIPTTAA STPDAVDKYL
ETPGDENEHA HFQKAKERLE AKHRERMSQV MREWEEAERQ AKNLPKADKK AVIQHFQEKV
ESLEQEAANE RQQLVETHMA RVEAMLNDRR RLALENYITA LQAVPPRPRH VFNMLKKYVR
AEQKDRQHTL KHFEHVRMVD PKKAAQIRSQ VMTHLRVIYE RMNQSLSLLY NVPAVAEEIQ
DEVDELLQKE QNYSDDVLAN MISEPRISYG NDALMPSLTE TKTTVELLPV NGEFSLDDLQ
PWHSFGADSV PANTENEVEP VDARPAADRG LTTRPGSGLT NIKTEEISEV KMDAEFRHDS
GYEVHHQKLV FFGEDVGSNK GAIIGLMVGG VVIATVIVIT LVMLKKKQYT SIHHGVVEVD
AAVTPEERHL SKMQQNGYEN PTYKFFEQMQ N*
speed 0.36 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
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Problems