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 0.49 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