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 11.56 s - this script 8.070244 s

Results


genesymbolpredictionprobabilitymodelprediction
problem
splicingClinVaramino acid changesvariant typedbSNP IDprotein lengthfile
APPdisease_causing0.999999999584763simple_aaeaffectedA582Tsingle base exchangers63750066show file
APPdisease_causing0.999999999584763simple_aaeaffectedA657Tsingle base exchangers63750066show file
APPdisease_causing0.999999999584763simple_aaeaffectedA638Tsingle base exchangers63750066show file
APPdisease_causing0.999999999584763simple_aaeaffectedA657Tsingle base exchangers63750066show file
APPdisease_causing0.999999999584763simple_aaeaffectedA603Tsingle base exchangers63750066show file
APPdisease_causing0.999999999737651simple_aaeaffectedA694Tsingle base exchangers63750066show file
APPdisease_causing0.999999999942075simple_aaeaffectedA689Tsingle base exchangers63750066show file
APPdisease_causing0.999999999956953simple_aaeaffectedA695Tsingle base exchangers63750066show file
APPdisease_causing0.999999999999965simple_aaeaffectedA713Tsingle base exchangers63750066show file

Taster files

Yum, tasty mutations...

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999999584763      (explain)
Summary
  • amino acid sequence changed
  • known as potential disease variant: rs18094 (probable pathogenic)
  • known disease mutation at this position (HGMD CM930033)
  • protein features (might be) affected
  • splice site changes
hyperlink
analysed issue analysis result
name of alteration no title
alteration (phys. location) chr21:27264108C>TN/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.1744G>A
cDNA.1871G>A
g.279339G>A
AA changes A582T Score: 58 explain score(s)
position(s) of altered AA
if AA alteration in CDS
582
frameshift no
known variant Reference ID: rs63750066
databasehomozygous (T/T)heterozygousallele carriers
1000G011
ExAC077

known as potential disease variant: rs18094 (probable pathogenic for Alzheimer disease|Alzheimer disease, type 1|Primary degenerative dementia of the Alzheimer type, presenile onset|not provided) dbSNP  NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)

known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)
known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)
regulatory features H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
phyloP / phastCons
PhyloPPhastCons
(flanking)5.7321
5.7321
(flanking)2.1131
explain score(s) and/or inspect your position(s) in in UCSC Genome Browser
splice sites
effectgDNA positionscorewt detection sequence exon-intron border
Donor marginally increased279344wt: 0.7349 / mu: 0.7640 (marginal change - not scored)wt: GCGACAGTGATCGTC
mu: ACGACAGTGATCGTC
 GACA|gtga
Donor gained2793390.76mu: TCATAACGACAGTGA ATAA|cgac
Donor gained2793400.35mu: CATAACGACAGTGAT TAAC|gaca
distance from splice site 73
Kozak consensus sequence altered? N/A
conservation
protein level for non-synonymous changes
speciesmatchgeneaaalignment
Human      582IIGLMVGGVVIATVIVITLVMLKK
mutated  not conserved    582IIGLMVGGVVITTVIVITLVMLK
Ptroglodytes  all identical  ENSPTRG00000013811  713IIGLMVGGVVIATVIVITLVMLK
Mmulatta  all identical  ENSMMUG00000014384  713IIGLMVGGVVIATVIVITLVMLK
Fcatus  all identical  ENSFCAG00000001556  694IIGLMVGGVVIATVIVITLVMLK
Mmusculus  all identical  ENSMUSG00000022892  638IIGLMVGGVVIATVIVITLVMLK
Ggallus  all identical  ENSGALG00000015770  694IIGLMVGGVVIATVIVITLVMLK
Trubripes  all identical  ENSTRUG00000010470  707IIGLMVGGVVIATVIVITLVMLR
Drerio  all identical  ENSDARG00000055543  694IIGLMVGGVVIATVIVITLVMLR
Dmelanogaster  no alignment  FBgn0000108  n/a
Celegans  not conserved  C42D8.8  631FQPYVLASAMFITAICIIAFAIT
Xtropicalis  all identical  ENSXETG00000013612  714IIGLMVGGVVIATVIVITLVMLK
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 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 1744
cDNA position
(for ins/del: last normal base / first normal base)
1871
gDNA position
(for ins/del: last normal base / first normal base)
279339
chromosomal position
(for ins/del: last normal base / first normal base)
27264108
original gDNA sequence snippet TGGTGGGCGGTGTTGTCATAGCGACAGTGATCGTCATCACC
altered gDNA sequence snippet TGGTGGGCGGTGTTGTCATAACGACAGTGATCGTCATCACC
original cDNA sequence snippet TGGTGGGCGGTGTTGTCATAGCGACAGTGATCGTCATCACC
altered cDNA sequence snippet TGGTGGGCGGTGTTGTCATAACGACAGTGATCGTCATCACC
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 AEDVGSNKGA IIGLMVGGVV ITTVIVITLV MLKKKQYTSI
HHGVVEVDAA VTPEERHLSK MQQNGYENPT YKFFEQMQN*
speed 1.46 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: 0.999999999584763      (explain)
Summary
  • amino acid sequence changed
  • known as potential disease variant: rs18094 (probable pathogenic)
  • known disease mutation at this position (HGMD CM930033)
  • protein features (might be) affected
  • splice site changes
hyperlink
analysed issue analysis result
name of alteration no title
alteration (phys. location) chr21:27264108C>TN/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.1969G>A
cDNA.2003G>A
g.279339G>A
AA changes A657T Score: 58 explain score(s)
position(s) of altered AA
if AA alteration in CDS
657
frameshift no
known variant Reference ID: rs63750066
databasehomozygous (T/T)heterozygousallele carriers
1000G011
ExAC077

known as potential disease variant: rs18094 (probable pathogenic for Alzheimer disease|Alzheimer disease, type 1|Primary degenerative dementia of the Alzheimer type, presenile onset|not provided) dbSNP  NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)

known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)
known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)
regulatory features H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
phyloP / phastCons
PhyloPPhastCons
(flanking)5.7321
5.7321
(flanking)2.1131
explain score(s) and/or inspect your position(s) in in UCSC Genome Browser
splice sites
effectgDNA positionscorewt detection sequence exon-intron border
Donor marginally increased279344wt: 0.7349 / mu: 0.7640 (marginal change - not scored)wt: GCGACAGTGATCGTC
mu: ACGACAGTGATCGTC
 GACA|gtga
Donor gained2793390.76mu: TCATAACGACAGTGA ATAA|cgac
Donor gained2793400.35mu: CATAACGACAGTGAT TAAC|gaca
distance from splice site 73
Kozak consensus sequence altered? N/A
conservation
protein level for non-synonymous changes
speciesmatchgeneaaalignment
Human      657IIGLMVGGVVIATVIVITLVMLKK
mutated  not conserved    657IIGLMVGGVVITTVI
Ptroglodytes  all identical  ENSPTRG00000013811  713IIGLMVGGVVIATVIVITLVMLK
Mmulatta  all identical  ENSMMUG00000014384  713IIGLMVGGVVIATVIVITLVMLK
Fcatus  all identical  ENSFCAG00000001556  694IIGLMVGGVVIATVIVITLVMLK
Mmusculus  all identical  ENSMUSG00000022892  638IIGLMVGGVVIATVIVITLVMLK
Ggallus  all identical  ENSGALG00000015770  694IIGLMVGGVVIATVIVITLVMLK
Trubripes  all identical  ENSTRUG00000010470  707IIGLMVGGVVIATVIVITLVMLR
Drerio  all identical  ENSDARG00000055543  698IIGLMVGGVVIATVIVITL
Dmelanogaster  no alignment  FBgn0000108  n/a
Celegans  not conserved  C42D8.8  630FQPYVLASAMFITAICIIAFAIT
Xtropicalis  all identical  ENSXETG00000013612  714IIGLMVGGVVIATVIVITLVMLK
protein features
start (aa)end (aa)featuredetails 
18699TOPO_DOMExtracellular (Potential).lost
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)
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)
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->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)
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)
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)
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 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 1969
cDNA position
(for ins/del: last normal base / first normal base)
2003
gDNA position
(for ins/del: last normal base / first normal base)
279339
chromosomal position
(for ins/del: last normal base / first normal base)
27264108
original gDNA sequence snippet TGGTGGGCGGTGTTGTCATAGCGACAGTGATCGTCATCACC
altered gDNA sequence snippet TGGTGGGCGGTGTTGTCATAACGACAGTGATCGTCATCACC
original cDNA sequence snippet TGGTGGGCGGTGTTGTCATAGCGACAGTGATCGTCATCACC
altered cDNA sequence snippet TGGTGGGCGGTGTTGTCATAACGACAGTGATCGTCATCACC
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 KLVFFAEDVG SNKGAIIGLM VGGVVITTVI
VITLVMLKKK QYTSIHHGVV EVDAAVTPEE RHLSKMQQNG YENPTYKFFE QMQN*
speed 1.21 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: 0.999999999584763      (explain)
Summary
  • amino acid sequence changed
  • known as potential disease variant: rs18094 (probable pathogenic)
  • known disease mutation at this position (HGMD CM930033)
  • protein features (might be) affected
  • splice site changes
hyperlink
analysed issue analysis result
name of alteration no title
alteration (phys. location) chr21:27264108C>TN/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.1912G>A
cDNA.2059G>A
g.279339G>A
AA changes A638T Score: 58 explain score(s)
position(s) of altered AA
if AA alteration in CDS
638
frameshift no
known variant Reference ID: rs63750066
databasehomozygous (T/T)heterozygousallele carriers
1000G011
ExAC077

known as potential disease variant: rs18094 (probable pathogenic for Alzheimer disease|Alzheimer disease, type 1|Primary degenerative dementia of the Alzheimer type, presenile onset|not provided) dbSNP  NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)

known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)
known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)
regulatory features H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
phyloP / phastCons
PhyloPPhastCons
(flanking)5.7321
5.7321
(flanking)2.1131
explain score(s) and/or inspect your position(s) in in UCSC Genome Browser
splice sites
effectgDNA positionscorewt detection sequence exon-intron border
Donor marginally increased279344wt: 0.7349 / mu: 0.7640 (marginal change - not scored)wt: GCGACAGTGATCGTC
mu: ACGACAGTGATCGTC
 GACA|gtga
Donor gained2793390.76mu: TCATAACGACAGTGA ATAA|cgac
Donor gained2793400.35mu: CATAACGACAGTGAT TAAC|gaca
distance from splice site 73
Kozak consensus sequence altered? N/A
conservation
protein level for non-synonymous changes
speciesmatchgeneaaalignment
Human      638IIGLMVGGVVIATVIVITLVMLKK
mutated  not conserved    638IIGLMVGGVVITTVIVITLVMLK
Ptroglodytes  all identical  ENSPTRG00000013811  713IIGLMVGGVVIATVIVITL
Mmulatta  all identical  ENSMMUG00000014384  713IIGLMVGGVVIATVIVITL
Fcatus  all identical  ENSFCAG00000001556  694IIGLMVGGVVIATVIVITLVMLK
Mmusculus  all identical  ENSMUSG00000022892  638IIGLMVGGVVIATVIVITLVMLK
Ggallus  all identical  ENSGALG00000015770  694IIGLMVGGVVIATVIVITLVMLK
Trubripes  all identical  ENSTRUG00000010470  707IIGLMVGGVVIATVIVITLVM
Drerio  all identical  ENSDARG00000055543  694IIGLMVGGVVIATVIVITLVMLR
Dmelanogaster  no alignment  FBgn0000108  n/a
Celegans  not conserved  C42D8.8  631ASAMFITAICIIAFAIT
Xtropicalis  all identical  ENSXETG00000013612  714IIGLMVGGVVIATVIVIT
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 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 1912
cDNA position
(for ins/del: last normal base / first normal base)
2059
gDNA position
(for ins/del: last normal base / first normal base)
279339
chromosomal position
(for ins/del: last normal base / first normal base)
27264108
original gDNA sequence snippet TGGTGGGCGGTGTTGTCATAGCGACAGTGATCGTCATCACC
altered gDNA sequence snippet TGGTGGGCGGTGTTGTCATAACGACAGTGATCGTCATCACC
original cDNA sequence snippet TGGTGGGCGGTGTTGTCATAGCGACAGTGATCGTCATCACC
altered cDNA sequence snippet TGGTGGGCGGTGTTGTCATAACGACAGTGATCGTCATCACC
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 QKLVFFAEDV GSNKGAIIGL MVGGVVITTV IVITLVMLKK KQYTSIHHGV
VEVDAAVTPE ERHLSKMQQN GYENPTYKFF EQMQN*
speed 1.12 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: 0.999999999584763      (explain)
Summary
  • amino acid sequence changed
  • known as potential disease variant: rs18094 (probable pathogenic)
  • known disease mutation at this position (HGMD CM930033)
  • protein features (might be) affected
  • splice site changes
hyperlink
analysed issue analysis result
name of alteration no title
alteration (phys. location) chr21:27264108C>TN/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.1969G>A
cDNA.2169G>A
g.279339G>A
AA changes A657T Score: 58 explain score(s)
position(s) of altered AA
if AA alteration in CDS
657
frameshift no
known variant Reference ID: rs63750066
databasehomozygous (T/T)heterozygousallele carriers
1000G011
ExAC077

known as potential disease variant: rs18094 (probable pathogenic for Alzheimer disease|Alzheimer disease, type 1|Primary degenerative dementia of the Alzheimer type, presenile onset|not provided) dbSNP  NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)

known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)
known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)
regulatory features H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
phyloP / phastCons
PhyloPPhastCons
(flanking)5.7321
5.7321
(flanking)2.1131
explain score(s) and/or inspect your position(s) in in UCSC Genome Browser
splice sites
effectgDNA positionscorewt detection sequence exon-intron border
Donor marginally increased279344wt: 0.7349 / mu: 0.7640 (marginal change - not scored)wt: GCGACAGTGATCGTC
mu: ACGACAGTGATCGTC
 GACA|gtga
Donor gained2793390.76mu: TCATAACGACAGTGA ATAA|cgac
Donor gained2793400.35mu: CATAACGACAGTGAT TAAC|gaca
distance from splice site 73
Kozak consensus sequence altered? N/A
conservation
protein level for non-synonymous changes
speciesmatchgeneaaalignment
Human      657IIGLMVGGVVIATVIVITLVMLKK
mutated  not conserved    657IIGLMVGGVVITTVI
Ptroglodytes  all identical  ENSPTRG00000013811  713IIGLMVGGVVIATVIVITL
Mmulatta  all identical  ENSMMUG00000014384  713IIGLMVGGVVIATVIVITL
Fcatus  all identical  ENSFCAG00000001556  694IIGLMVGGVVIATVIVITLVMLK
Mmusculus  all identical  ENSMUSG00000022892  638IIGLMVGGVVIATVI
Ggallus  all identical  ENSGALG00000015770  694IIGLMVGGVVIATVIVITLVMLK
Trubripes  all identical  ENSTRUG00000010470  707IIGLMVGGVVIATVIVITLVM
Drerio  all identical  ENSDARG00000055543  694IIGLMVGGVVIATVIVITLVMLR
Dmelanogaster  no alignment  FBgn0000108  n/a
Celegans  not conserved  C42D8.8  631FQPYVLASAMFITAICIIAFAIT
Xtropicalis  all identical  ENSXETG00000013612  714IIGLMVGGVVIATVIVIT
protein features
start (aa)end (aa)featuredetails 
18699TOPO_DOMExtracellular (Potential).lost
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)
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)
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->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)
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)
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)
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 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 1969
cDNA position
(for ins/del: last normal base / first normal base)
2169
gDNA position
(for ins/del: last normal base / first normal base)
279339
chromosomal position
(for ins/del: last normal base / first normal base)
27264108
original gDNA sequence snippet TGGTGGGCGGTGTTGTCATAGCGACAGTGATCGTCATCACC
altered gDNA sequence snippet TGGTGGGCGGTGTTGTCATAACGACAGTGATCGTCATCACC
original cDNA sequence snippet TGGTGGGCGGTGTTGTCATAGCGACAGTGATCGTCATCACC
altered cDNA sequence snippet TGGTGGGCGGTGTTGTCATAACGACAGTGATCGTCATCACC
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 KLVFFAEDVG SNKGAIIGLM VGGVVITTVI
VITLVMLKKK QYTSIHHGVV EVDAAVTPEE RHLSKMQQNG YENPTYKFFE QMQN*
speed 1.07 s
All positions are in basepairs (bp) if not explicitly stated differently.
AA/aa: amino acid; CDS: coding sequence; mu: mutated; NMD: nonsense-mediated mRNA decay; nt: nucleotide; wt: wildtype; TGP: 1000 Genomes Project
back to results table
Yum, tasty mutations...

mutation t@sting

documentation

Prediction

disease causing

Model: simple_aae, prob: 0.999999999584763      (explain)
Summary
  • amino acid sequence changed
  • known as potential disease variant: rs18094 (probable pathogenic)
  • known disease mutation at this position (HGMD CM930033)
  • protein features (might be) affected
  • splice site changes
hyperlink
analysed issue analysis result
name of alteration no title
alteration (phys. location) chr21:27264108C>TN/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.1807G>A
cDNA.1999G>A
g.279339G>A
AA changes A603T Score: 58 explain score(s)
position(s) of altered AA
if AA alteration in CDS
603
frameshift no
known variant Reference ID: rs63750066
databasehomozygous (T/T)heterozygousallele carriers
1000G011
ExAC077

known as potential disease variant: rs18094 (probable pathogenic for Alzheimer disease|Alzheimer disease, type 1|Primary degenerative dementia of the Alzheimer type, presenile onset|not provided) dbSNP  NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)

known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)
known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)
regulatory features H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
phyloP / phastCons
PhyloPPhastCons
(flanking)5.7321
5.7321
(flanking)2.1131
explain score(s) and/or inspect your position(s) in in UCSC Genome Browser
splice sites
effectgDNA positionscorewt detection sequence exon-intron border
Donor marginally increased279344wt: 0.7349 / mu: 0.7640 (marginal change - not scored)wt: GCGACAGTGATCGTC
mu: ACGACAGTGATCGTC
 GACA|gtga
Donor gained2793390.76mu: TCATAACGACAGTGA ATAA|cgac
Donor gained2793400.35mu: CATAACGACAGTGAT TAAC|gaca
distance from splice site 73
Kozak consensus sequence altered? N/A
conservation
protein level for non-synonymous changes
speciesmatchgeneaaalignment
Human      603IIGLMVGGVVIATVIVITLVMLKK
mutated  not conserved    603VITTVIVITLVMLK
Ptroglodytes  all identical  ENSPTRG00000013811  713IIGLMVGGVVIATVIVITLVMLK
Mmulatta  all identical  ENSMMUG00000014384  713IIGLMVGGVVIATVIVITLVMLK
Fcatus  all identical  ENSFCAG00000001556  694IIGLMVGGVVIATVIVITLVMLK
Mmusculus  all identical  ENSMUSG00000022892  638VIATVIVITLVMLK
Ggallus  all identical  ENSGALG00000015770  694ATVIVITLVMLK
Trubripes  all identical  ENSTRUG00000010470  707IIGLMVGGVVIATVIVITLVMLR
Drerio  all identical  ENSDARG00000055543  694IIGLMVGGVVIATVIVITLVMLR
Dmelanogaster  no alignment  FBgn0000108  n/a
Celegans  not conserved  C42D8.8  630FQPYVLASAMFITAICIIAFAIT
Xtropicalis  all identical  ENSXETG00000013612  714IIGLMVGGVVIATVIVITLVMLK
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 1807
cDNA position
(for ins/del: last normal base / first normal base)
1999
gDNA position
(for ins/del: last normal base / first normal base)
279339
chromosomal position
(for ins/del: last normal base / first normal base)
27264108
original gDNA sequence snippet TGGTGGGCGGTGTTGTCATAGCGACAGTGATCGTCATCACC
altered gDNA sequence snippet TGGTGGGCGGTGTTGTCATAACGACAGTGATCGTCATCACC
original cDNA sequence snippet TGGTGGGCGGTGTTGTCATAGCGACAGTGATCGTCATCACC
altered cDNA sequence snippet TGGTGGGCGGTGTTGTCATAACGACAGTGATCGTCATCACC
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 FAEDVGSNKG AIIGLMVGGV
VITTVIVITL VMLKKKQYTS IHHGVVEVDA AVTPEERHLS KMQQNGYENP TYKFFEQMQN
*
speed 1.16 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: 0.999999999737651      (explain)
Summary
  • amino acid sequence changed
  • known as potential disease variant: rs18094 (probable pathogenic)
  • known disease mutation at this position (HGMD CM930033)
  • protein features (might be) affected
  • splice site changes
hyperlink
analysed issue analysis result
name of alteration no title
alteration (phys. location) chr21:27264108C>TN/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.2080G>A
cDNA.2247G>A
g.279339G>A
AA changes A694T Score: 58 explain score(s)
position(s) of altered AA
if AA alteration in CDS
694
frameshift no
known variant Reference ID: rs63750066
databasehomozygous (T/T)heterozygousallele carriers
1000G011
ExAC077

known as potential disease variant: rs18094 (probable pathogenic for Alzheimer disease|Alzheimer disease, type 1|Primary degenerative dementia of the Alzheimer type, presenile onset|not provided) dbSNP  NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)

known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)
known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)
regulatory features H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
phyloP / phastCons
PhyloPPhastCons
(flanking)5.7321
5.7321
(flanking)2.1131
explain score(s) and/or inspect your position(s) in in UCSC Genome Browser
splice sites
effectgDNA positionscorewt detection sequence exon-intron border
Donor marginally increased279344wt: 0.7349 / mu: 0.7640 (marginal change - not scored)wt: GCGACAGTGATCGTC
mu: ACGACAGTGATCGTC
 GACA|gtga
Donor gained2793390.76mu: TCATAACGACAGTGA ATAA|cgac
Donor gained2793400.35mu: CATAACGACAGTGAT TAAC|gaca
distance from splice site 73
Kozak consensus sequence altered? N/A
conservation
protein level for non-synonymous changes
speciesmatchgeneaaalignment
Human      694IIGLMVGGVVIATVIVITLVMLKK
mutated  not conserved    694IIGLMVGGVVITTVIVITLVMLK
Ptroglodytes  all identical  ENSPTRG00000013811  713IIGLMVGGVVIATVIVITL
Mmulatta  all identical  ENSMMUG00000014384  713IIGLMVGGVVIATVIVITL
Fcatus  all identical  ENSFCAG00000001556  694IIGLMVGGVVIATVIVITLVMLK
Mmusculus  all identical  ENSMUSG00000022892  638IIGLMVGGVVIATVIVITLVMLK
Ggallus  all identical  ENSGALG00000015770  694IIGLMVGGVVIATVIVITLVMLK
Trubripes  all identical  ENSTRUG00000010470  707IIGLMVGGVVIATVIVITLVM
Drerio  all identical  ENSDARG00000055543  694IIGLMVGGVVIATVIVITLVMLR
Dmelanogaster  no alignment  FBgn0000108  n/a
Celegans  not conserved  C42D8.8  631FQPYVLASAMFITAICIIAFAIT
Xtropicalis  all identical  ENSXETG00000013612  714IIGLMVGGVVIATVIVIT
protein features
start (aa)end (aa)featuredetails 
18699TOPO_DOMExtracellular (Potential).lost
688711PEPTIDEP3(40). /FTId=PRO_0000000096.lost
688713PEPTIDEP3(42). /FTId=PRO_0000000095.lost
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->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->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)
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)
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; 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)
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)
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 2080
cDNA position
(for ins/del: last normal base / first normal base)
2247
gDNA position
(for ins/del: last normal base / first normal base)
279339
chromosomal position
(for ins/del: last normal base / first normal base)
27264108
original gDNA sequence snippet TGGTGGGCGGTGTTGTCATAGCGACAGTGATCGTCATCACC
altered gDNA sequence snippet TGGTGGGCGGTGTTGTCATAACGACAGTGATCGTCATCACC
original cDNA sequence snippet TGGTGGGCGGTGTTGTCATAGCGACAGTGATCGTCATCACC
altered cDNA sequence snippet TGGTGGGCGGTGTTGTCATAACGACAGTGATCGTCATCACC
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 FFAEDVGSNK GAIIGLMVGG VVITTVIVIT LVMLKKKQYT SIHHGVVEVD
AAVTPEERHL SKMQQNGYEN PTYKFFEQMQ N*
speed 1.66 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: 0.999999999942075      (explain)
Summary
  • amino acid sequence changed
  • known as potential disease variant: rs18094 (probable pathogenic)
  • known disease mutation at this position (HGMD CM930033)
  • protein features (might be) affected
  • splice site changes
hyperlink
analysed issue analysis result
name of alteration no title
alteration (phys. location) chr21:27264108C>TN/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.2065G>A
cDNA.2222G>A
g.279339G>A
AA changes A689T Score: 58 explain score(s)
position(s) of altered AA
if AA alteration in CDS
689
frameshift no
known variant Reference ID: rs63750066
databasehomozygous (T/T)heterozygousallele carriers
1000G011
ExAC077

known as potential disease variant: rs18094 (probable pathogenic for Alzheimer disease|Alzheimer disease, type 1|Primary degenerative dementia of the Alzheimer type, presenile onset|not provided) dbSNP  NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)

known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)
known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)
regulatory features H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
phyloP / phastCons
PhyloPPhastCons
(flanking)5.7321
5.7321
(flanking)2.1131
explain score(s) and/or inspect your position(s) in in UCSC Genome Browser
splice sites
effectgDNA positionscorewt detection sequence exon-intron border
Donor marginally increased279344wt: 0.7349 / mu: 0.7640 (marginal change - not scored)wt: GCGACAGTGATCGTC
mu: ACGACAGTGATCGTC
 GACA|gtga
Donor gained2793390.76mu: TCATAACGACAGTGA ATAA|cgac
Donor gained2793400.35mu: CATAACGACAGTGAT TAAC|gaca
distance from splice site 73
Kozak consensus sequence altered? N/A
conservation
protein level for non-synonymous changes
speciesmatchgeneaaalignment
Human      689IIGLMVGGVVIATVIVITLVMLKK
mutated  not conserved    689IIGLMVGGVVITTVIVITLVMLK
Ptroglodytes  all identical  ENSPTRG00000013811  713IIGLMVGGVVIATVIVITLVMLK
Mmulatta  all identical  ENSMMUG00000014384  713IIGLMVGGVVIATVIVITLVMLK
Fcatus  all identical  ENSFCAG00000001556  694IIGLMVGGVVIATVIVITLVMLK
Mmusculus  all identical  ENSMUSG00000022892  638IIGLMVGGVVIATVIVITLVMLK
Ggallus  all identical  ENSGALG00000015770  694IIGLMVGGVVIATVIVITLVMLK
Trubripes  all identical  ENSTRUG00000010470  707IIGLMVGGVVIATVIVITLVMLR
Drerio  all identical  ENSDARG00000055543  694IIGLMVGGVVIATVIVITLVMLR
Dmelanogaster  no alignment  FBgn0000108  n/a
Celegans  not conserved  C42D8.8  631FQPYVLASAMFITAICIIAFAIT
Xtropicalis  all identical  ENSXETG00000013612  714IIGLMVGGVVIATVIVITLVMLK
protein features
start (aa)end (aa)featuredetails 
18699TOPO_DOMExtracellular (Potential).lost
688691STRANDlost
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 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 2065
cDNA position
(for ins/del: last normal base / first normal base)
2222
gDNA position
(for ins/del: last normal base / first normal base)
279339
chromosomal position
(for ins/del: last normal base / first normal base)
27264108
original gDNA sequence snippet TGGTGGGCGGTGTTGTCATAGCGACAGTGATCGTCATCACC
altered gDNA sequence snippet TGGTGGGCGGTGTTGTCATAACGACAGTGATCGTCATCACC
original cDNA sequence snippet TGGTGGGCGGTGTTGTCATAGCGACAGTGATCGTCATCACC
altered cDNA sequence snippet TGGTGGGCGGTGTTGTCATAACGACAGTGATCGTCATCACC
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
HQKLVFFAED VGSNKGAIIG LMVGGVVITT VIVITLVMLK KKQYTSIHHG VVEVDAAVTP
EERHLSKMQQ NGYENPTYKF FEQMQN*
speed 1.14 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: 0.999999999956953      (explain)
Summary
  • amino acid sequence changed
  • known as potential disease variant: rs18094 (probable pathogenic)
  • known disease mutation at this position (HGMD CM930033)
  • protein features (might be) affected
  • splice site changes
hyperlink
analysed issue analysis result
name of alteration no title
alteration (phys. location) chr21:27264108C>TN/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.2083G>A
cDNA.2283G>A
g.279339G>A
AA changes A695T Score: 58 explain score(s)
position(s) of altered AA
if AA alteration in CDS
695
frameshift no
known variant Reference ID: rs63750066
databasehomozygous (T/T)heterozygousallele carriers
1000G011
ExAC077

known as potential disease variant: rs18094 (probable pathogenic for Alzheimer disease|Alzheimer disease, type 1|Primary degenerative dementia of the Alzheimer type, presenile onset|not provided) dbSNP  NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)

known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)
known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)
regulatory features H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
phyloP / phastCons
PhyloPPhastCons
(flanking)5.7321
5.7321
(flanking)2.1131
explain score(s) and/or inspect your position(s) in in UCSC Genome Browser
splice sites
effectgDNA positionscorewt detection sequence exon-intron border
Donor marginally increased279344wt: 0.7349 / mu: 0.7640 (marginal change - not scored)wt: GCGACAGTGATCGTC
mu: ACGACAGTGATCGTC
 GACA|gtga
Donor gained2793390.76mu: TCATAACGACAGTGA ATAA|cgac
Donor gained2793400.35mu: CATAACGACAGTGAT TAAC|gaca
distance from splice site 73
Kozak consensus sequence altered? N/A
conservation
protein level for non-synonymous changes
speciesmatchgeneaaalignment
Human      695IIGLMVGGVVIATVIVITLVMLKK
mutated  not conserved    695IIGLMVGGVVITTVIVITLVMLK
Ptroglodytes  all identical  ENSPTRG00000013811  713IIGLMVGGVVIATVIVITL
Mmulatta  all identical  ENSMMUG00000014384  713IIGLMVGGVVIATVIVITL
Fcatus  all identical  ENSFCAG00000001556  694IIGLMVGGVVIATVIVITLVMLK
Mmusculus  all identical  ENSMUSG00000022892  638IIGLMVGGVVIATVIVITL
Ggallus  all identical  ENSGALG00000015770  694IIGLMVGGVVIATVIVI
Trubripes  all identical  ENSTRUG00000010470  707IIGLMVGGVVIATVIVITLVMLR
Drerio  all identical  ENSDARG00000055543  693IIGLMVGGVVIATVIVITLVM
Dmelanogaster  no alignment  FBgn0000108  n/a
Celegans  not conserved  C42D8.8  630FQPYVLASAMFITAICIIAFAIT
Xtropicalis  all identical  ENSXETG00000013612  714IIGLMVGGVVIATVIVIT
protein features
start (aa)end (aa)featuredetails 
18699TOPO_DOMExtracellular (Potential).lost
688711PEPTIDEP3(40). /FTId=PRO_0000000096.lost
688713PEPTIDEP3(42). /FTId=PRO_0000000095.lost
695697HELIXlost
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->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->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)
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)
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; 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)
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)
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 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 2083
cDNA position
(for ins/del: last normal base / first normal base)
2283
gDNA position
(for ins/del: last normal base / first normal base)
279339
chromosomal position
(for ins/del: last normal base / first normal base)
27264108
original gDNA sequence snippet TGGTGGGCGGTGTTGTCATAGCGACAGTGATCGTCATCACC
altered gDNA sequence snippet TGGTGGGCGGTGTTGTCATAACGACAGTGATCGTCATCACC
original cDNA sequence snippet TGGTGGGCGGTGTTGTCATAGCGACAGTGATCGTCATCACC
altered cDNA sequence snippet TGGTGGGCGGTGTTGTCATAACGACAGTGATCGTCATCACC
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 VFFAEDVGSN KGAIIGLMVG GVVITTVIVI TLVMLKKKQY TSIHHGVVEV
DAAVTPEERH LSKMQQNGYE NPTYKFFEQM QN*
speed 1.48 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: 0.999999999999965      (explain)
Summary
  • amino acid sequence changed
  • known as potential disease variant: rs18094 (probable pathogenic)
  • known disease mutation at this position (HGMD CM930033)
  • protein features (might be) affected
  • splice site changes
hyperlink
analysed issue analysis result
name of alteration no title
alteration (phys. location) chr21:27264108C>TN/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.2137G>A
cDNA.2171G>A
g.279339G>A
AA changes A713T Score: 58 explain score(s)
position(s) of altered AA
if AA alteration in CDS
713
frameshift no
known variant Reference ID: rs63750066
databasehomozygous (T/T)heterozygousallele carriers
1000G011
ExAC077

known as potential disease variant: rs18094 (probable pathogenic for Alzheimer disease|Alzheimer disease, type 1|Primary degenerative dementia of the Alzheimer type, presenile onset|not provided) dbSNP  NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)

known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)
known disease mutation at this position, please check HGMD for details (HGMD ID CM930033)
regulatory features H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
phyloP / phastCons
PhyloPPhastCons
(flanking)5.7321
5.7321
(flanking)2.1131
explain score(s) and/or inspect your position(s) in in UCSC Genome Browser
splice sites
effectgDNA positionscorewt detection sequence exon-intron border
Donor marginally increased279344wt: 0.7349 / mu: 0.7640 (marginal change - not scored)wt: GCGACAGTGATCGTC
mu: ACGACAGTGATCGTC
 GACA|gtga
Donor gained2793390.76mu: TCATAACGACAGTGA ATAA|cgac
Donor gained2793400.35mu: CATAACGACAGTGAT TAAC|gaca
distance from splice site 73
Kozak consensus sequence altered? N/A
conservation
protein level for non-synonymous changes
speciesmatchgeneaaalignment
Human      713IIGLMVGGVVIATVIVITLVMLKK
mutated  not conserved    713IIGLMVGGVVITTVIVITL
Ptroglodytes  all identical  ENSPTRG00000013811  713IIGLMVGGVVIATVIVITL
Mmulatta  all identical  ENSMMUG00000014384  713IIGLMVGGVVIATVIVITL
Fcatus  all identical  ENSFCAG00000001556  694IIGLMVGGVVIATVIVITLVMLK
Mmusculus  all identical  ENSMUSG00000022892  638IIGLMVGGVVIATVIVITL
Ggallus  all identical  ENSGALG00000015770  694IIGLMVGGVVIATVIVI
Trubripes  all identical  ENSTRUG00000010470  707IIGLMVGGVVIATVIVITLVM
Drerio  all identical  ENSDARG00000055543  694ATVIVITLVMLR
Dmelanogaster  no alignment  FBgn0000108  n/a
Celegans  not conserved  C42D8.8  630FQPYVLASAMFITAICIIAFAIT
Xtropicalis  all identical  ENSXETG00000013612  714IIGLMVGGVVIATVIVIT
protein features
start (aa)end (aa)featuredetails 
688713PEPTIDEP3(42). /FTId=PRO_0000000095.lost
700723TRANSMEMHelical; (Potential).lost
713714SITECleavage; by gamma-secretase; site 2.lost
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->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)
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)
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)
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 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 2137
cDNA position
(for ins/del: last normal base / first normal base)
2171
gDNA position
(for ins/del: last normal base / first normal base)
279339
chromosomal position
(for ins/del: last normal base / first normal base)
27264108
original gDNA sequence snippet TGGTGGGCGGTGTTGTCATAGCGACAGTGATCGTCATCACC
altered gDNA sequence snippet TGGTGGGCGGTGTTGTCATAACGACAGTGATCGTCATCACC
original cDNA sequence snippet TGGTGGGCGGTGTTGTCATAGCGACAGTGATCGTCATCACC
altered cDNA sequence snippet TGGTGGGCGGTGTTGTCATAACGACAGTGATCGTCATCACC
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 FAEDVGSNKG AIIGLMVGGV VITTVIVITL
VMLKKKQYTS IHHGVVEVDA AVTPEERHLS KMQQNGYENP TYKFFEQMQN *
speed 1.26 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

Problems