mutation t@sting

Prediction

disease causing

Model: simple_aae, prob: 0.999999999999924 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
known disease mutation at this position (HGMD CM042708)
known disease mutation at this position (HGMD CM065237)
known disease mutation at this position (HGMD CM146676)
known disease mutation: rs17031 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr13:20763590C>GN/A show variant in all transcripts IGV

HGNC symbol

GJB2

Ensembl transcript ID

ENST00000382844

Genbank transcript ID

N/A

UniProt peptide

P29033

alteration type

single base exchange

alteration region

CDS

DNA changes

c.131G>C
cDNA.330G>C
g.3448G>C

AA changes

W44S Score: 177 explain score(s)

position(s) of altered AA
if AA alteration in CDS

frameshift

known variant

Reference ID: rs104894413
Allele 'G' was neither found in ExAC nor 1000G.
known disease mutation: rs17031 (pathogenic for Deafness, autosomal dominant 3a) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM042708)

known disease mutation at this position, please check HGMD for details (HGMD ID CM042708)
known disease mutation at this position, please check HGMD for details (HGMD ID CM065237)

known disease mutation at this position, please check HGMD for details (HGMD ID CM042708)
known disease mutation at this position, please check HGMD for details (HGMD ID CM065237)
known disease mutation at this position, please check HGMD for details (HGMD ID CM146676)

known disease mutation at this position, please check HGMD for details (HGMD ID CM042708)
known disease mutation at this position, please check HGMD for details (HGMD ID CM065237)
known disease mutation at this position, please check HGMD for details (HGMD ID CM146676)
known disease mutation at this position, please check HGMD for details (HGMD ID CM042708)

known disease mutation at this position, please check HGMD for details (HGMD ID CM042708)
known disease mutation at this position, please check HGMD for details (HGMD ID CM065237)
known disease mutation at this position, please check HGMD for details (HGMD ID CM146676)
known disease mutation at this position, please check HGMD for details (HGMD ID CM042708)
known disease mutation at this position, please check HGMD for details (HGMD ID CM065237)

regulatory features

Promoter Associated, Regulatory Feature, Promoter like regulatory feature
Max, Transcription Factor, Max TF binding
Gabp, Transcription Factor, Gabp TF binding
H3K27me3, Histone, Histone 3 Lysine 27 Tri-Methylation
H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation
Gene Associated, Regulatory Feature, Gene associated regulatory feature
CTCF, Transcription Factor, CCCTC-binding factor

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	6.028	1
	6.028	1
(flanking)	3.385	1

explain score(s) and/or inspect your position(s) in in UCSC Genome Browser

splice sites

effect	gDNA position	score	wt detection sequence	exon-intron border
Donor marginally increased	3440	wt: 0.8570 / mu: 0.9099 (marginal change - not scored)	wt: GCAAAGGAGGTGTGG mu: GCAAAGGAGGTGTCG	AAAG\|gagg
Donor increased	3450	wt: 0.75 / mu: 0.98	wt: TGTGGGGAGATGAGC mu: TGTCGGGAGATGAGC	TGGG\|gaga
Donor marginally increased	3452	wt: 0.9788 / mu: 0.9897 (marginal change - not scored)	wt: TGGGGAGATGAGCAG mu: TCGGGAGATGAGCAG	GGGA\|gatg

distance from splice site

330

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

mutated

not conserved

Ptroglodytes

all identical

ENSPTRG00000031248

Mmulatta

all identical

ENSMMUG00000010522

Fcatus

all identical

ENSFCAG00000006961

Mmusculus

all identical

ENSMUSG00000046352

Ggallus

all identical

ENSGALG00000017136

Trubripes

no homologue

Drerio

all identical

ENSDARG00000042707

Dmelanogaster

no homologue

Celegans

no homologue

Xtropicalis

all identical

ENSXETG00000026112

protein features

start (aa)	end (aa)	feature	details
41	75	TOPO_DOM	Extracellular (Potential).	lost
46	49	HELIX		might get lost (downstream of altered splice site)
52	54	STRAND		might get lost (downstream of altered splice site)
53	53	DISULFID		might get lost (downstream of altered splice site)
60	60	DISULFID		might get lost (downstream of altered splice site)
60	66	HELIX		might get lost (downstream of altered splice site)
64	64	DISULFID		might get lost (downstream of altered splice site)
73	83	HELIX		might get lost (downstream of altered splice site)
76	98	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
85	105	HELIX		might get lost (downstream of altered splice site)
86	86	CONFLICT	T -> S (in Ref. 1; AAD21314).	might get lost (downstream of altered splice site)
99	131	TOPO_DOM	Cytoplasmic (Potential).	might get lost (downstream of altered splice site)
106	108	TURN		might get lost (downstream of altered splice site)
112	112	CONFLICT	K -> N (in Ref. 4; AAY25170).	might get lost (downstream of altered splice site)
126	130	TURN		might get lost (downstream of altered splice site)
131	156	HELIX		might get lost (downstream of altered splice site)
132	154	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
155	192	TOPO_DOM	Extracellular (Potential).	might get lost (downstream of altered splice site)
157	159	TURN		might get lost (downstream of altered splice site)
160	162	STRAND		might get lost (downstream of altered splice site)
165	169	STRAND		might get lost (downstream of altered splice site)
169	169	DISULFID		might get lost (downstream of altered splice site)
174	174	DISULFID		might get lost (downstream of altered splice site)
174	181	STRAND		might get lost (downstream of altered splice site)
180	180	DISULFID		might get lost (downstream of altered splice site)
185	215	HELIX		might get lost (downstream of altered splice site)
193	215	TRANSMEM	Helical; (Potential).	might get lost (downstream of altered splice site)
216	226	TOPO_DOM	Cytoplasmic (Potential).	might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

681 / 681

position (AA) of stopcodon in wt / mu AA sequence

227 / 227

position of stopcodon in wt / mu cDNA

880 / 880

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

200 / 200

chromosome

strand

-1

last intron/exon boundary

theoretical NMD boundary in CDS

cannot be calculated, too little distance between start ATG and last intron/exon boundary

length of CDS

681

coding sequence (CDS) position

131

cDNA position
(for ins/del: last normal base / first normal base)

330

gDNA position
(for ins/del: last normal base / first normal base)

3448

chromosomal position
(for ins/del: last normal base / first normal base)

20763590

original gDNA sequence snippet

TGTGGCTGCAAAGGAGGTGTGGGGAGATGAGCAGGCCGACT

altered gDNA sequence snippet

TGTGGCTGCAAAGGAGGTGTCGGGAGATGAGCAGGCCGACT

original cDNA sequence snippet

TGTGGCTGCAAAGGAGGTGTGGGGAGATGAGCAGGCCGACT

altered cDNA sequence snippet

TGTGGCTGCAAAGGAGGTGTCGGGAGATGAGCAGGCCGACT

wildtype AA sequence

MDWGTLQTIL GGVNKHSTSI GKIWLTVLFI FRIMILVVAA KEVWGDEQAD FVCNTLQPGC
KNVCYDHYFP ISHIRLWALQ LIFVSTPALL VAMHVAYRRH EKKRKFIKGE IKSEFKDIEE
IKTQKVRIEG SLWWTYTSSI FFRVIFEAAF MYVFYVMYDG FSMQRLVKCN AWPCPNTVDC
FVSRPTEKTV FTVFMIAVSG ICILLNVTEL CYLLIRYCSG KSKKPV*

mutated AA sequence

MDWGTLQTIL GGVNKHSTSI GKIWLTVLFI FRIMILVVAA KEVSGDEQAD FVCNTLQPGC
KNVCYDHYFP ISHIRLWALQ LIFVSTPALL VAMHVAYRRH EKKRKFIKGE IKSEFKDIEE
IKTQKVRIEG SLWWTYTSSI FFRVIFEAAF MYVFYVMYDG FSMQRLVKCN AWPCPNTVDC
FVSRPTEKTV FTVFMIAVSG ICILLNVTEL CYLLIRYCSG KSKKPV*

speed

0.77 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