Yum, tasty mutations...

mutation t@sting

 documentation

Prediction

disease causing

 Model: simple_aae, prob: 0.999999999999961 (classification due to ClinVar, real probability is shown anyway)      (explain)
Summary
  • amino acid sequence changed
  • known disease mutation at this position (HGMD CM021245)
  • known disease mutation: rs18102 (pathogenic)
  • protein features (might be) affected
  • splice site changes
 hyperlink
analysed issue analysis result
name of alteration no title
alteration (phys. location) chr21:27264105T>CN/A show variant in all transcripts   IGV
HGNC symbol APP
Ensembl transcript ID ENST00000440126
Genbank transcript ID NM_001136016
UniProt peptide P05067
alteration type single base exchange
alteration region CDS
DNA changes c.2068A>G
cDNA.2225A>G
g.279342A>G
AA changes T690A Score: 58 explain score(s)
position(s) of altered AA
if AA alteration in CDS		 690
frameshift no
known variant Reference ID: rs63750643
Allele 'C' was neither found in ExAC nor 1000G.
known disease mutation: rs18102 (pathogenic for Alzheimer disease, type 1|not provided) dbSNP  NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM021245)

known disease mutation at this position, please check HGMD for details (HGMD ID CM021245)
known disease mutation at this position, please check HGMD for details (HGMD ID CM021245)
regulatory features H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
phyloP / phastCons
PhyloPPhastCons
(flanking)5.7321
4.7451
(flanking)0.0760.996
explain score(s) and/or inspect your position(s) in in UCSC Genome Browser
splice sites
effectgDNA positionscorewt detection sequence exon-intron border
Donor gained2793410.43mu: ATAGCGGCAGTGATC AGCG|gcag
distance from splice site 72
Kozak consensus sequence altered? N/A
conservation
protein level for non-synonymous changes
speciesmatchgeneaaalignment
Human      690IGLMVGGVVIATVIVITLVMLKKK
mutated  not conserved    690IGLMVGGVVIAAVIVITLVMLKK
Ptroglodytes  all identical  ENSPTRG00000013811  714IGLMVGGVVIATVIVITLVMLKK
Mmulatta  all identical  ENSMMUG00000014384  714IGLMVGGVVIATVIVITLVMLKK
Fcatus  all identical  ENSFCAG00000001556  695IGLMVGGVVIATVIVITLVMLK
Mmusculus  all identical  ENSMUSG00000022892  639IGLMVGGVVIATVIVITLVMLKK
Ggallus  all identical  ENSGALG00000015770  695IGLMVGGVVIATVIVITLVMLKK
Trubripes  all identical  ENSTRUG00000010470  708IGLMVGGVVIATVIVITLVMLRK
Drerio  all identical  ENSDARG00000055543  695IGLMVGGVVIATVIVITLVMLRK
Dmelanogaster  no alignment  FBgn0000108  n/a
Celegans  all identical  C42D8.8  632QPYVLASAMFITAICIIAFAITN
Xtropicalis  all identical  ENSXETG00000013612  715IGLMVGGVVIATVIVITLVMLKK
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.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)
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 2068
cDNA position
(for ins/del: last normal base / first normal base)		 2225
gDNA position
(for ins/del: last normal base / first normal base)		 279342
chromosomal position
(for ins/del: last normal base / first normal base)		 27264105
original gDNA sequence snippet TGGGCGGTGTTGTCATAGCGACAGTGATCGTCATCACCTTG
altered gDNA sequence snippet TGGGCGGTGTTGTCATAGCGGCAGTGATCGTCATCACCTTG
original cDNA sequence snippet TGGGCGGTGTTGTCATAGCGACAGTGATCGTCATCACCTTG
altered cDNA sequence snippet TGGGCGGTGTTGTCATAGCGGCAGTGATCGTCATCACCTTG
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 LMVGGVVIAA VIVITLVMLK KKQYTSIHHG VVEVDAAVTP
EERHLSKMQQ NGYENPTYKF FEQMQN*
speed 0.99 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