IGDRPT (Indian Genetic Disease Risk Prediction Tool)

Disease Name: Rett Syndrome

1 .Inheritance

X-linked Dominants

2. Gene Name

MECP2

3. Protein Name

Methyl-CpG-binding protein 2

4. Chromosomal Location

Xq28

5. Protein Sequence

>sp|P51608|MECP2_HUMAN Methyl-CpG-binding protein 2 OS=Homo sapiens OX=9606 GN=MECP2 PE=1 SV=1

MVAGMLGLREEKSEDQDLQGLKDKPLKFKKVKKDKKEEKEGKHEPVQPSAHHSAEPAEAG

KAETSEGSGSAPAVPEASASPKQRRSIIRDRGPMYDDPTLPEGWTRKLKQRKSGRSAGKY

DVYLINPQGKAFRSKVELIAYFEKVGDTSLDPNDFDFTVTGRGSPSRREQKPPKKPKSPK

APGTGRGRGRPKGSGTTRPKAATSEGVQVKRVLEKSPGKLLVKMPFQTSPGGKAEGGGAT

TSTQVMVIKRPGRKRKAEADPQAIPKKRGRKPGSVVAAAAAEAKKKAVKESSIRSVQETV

LPIKKRKTRETVSIEVKEVVKPLLVSTLGEKSGKGLKTCKSPGRKSKESSPKGRSSSASS

PPKKEHHHHHHHSESPKAPVPLLPPLPPPPPEPESSEDPTSPPEPQDLSSSVCKEEKMPR

GGSLESDGCPKEPAKTQPAVATAATAAEKYKHRGEGERKDIVSSSMPRPNREEPVDSRTP

VTERVS

6. Gene Sequence

>NM_001110792.1 Homo sapiens methyl-CpG binding protein 2 (MECP2), transcript variant 2, mRNA

CCGGCGTCGGCGGCGCGCGCGCTCCCTCCTCTCGGAGAGAGGGCTGTGGTAAAAGCCGTCCGGAAAATGG

CCGCCGCCGCCGCCGCCGCGCCGAGCGGAGGAGGAGGAGGAGGCGAGGAGGAGAGACTGGAAGAAAAGTC

AGAAGACCAGGACCTCCAGGGCCTCAAGGACAAACCCCTCAAGTTTAAAAAGGTGAAGAAAGATAAGAAA

GAAGAGAAAGAGGGCAAGCATGAGCCCGTGCAGCCATCAGCCCACCACTCTGCTGAGCCCGCAGAGGCAG

GCAAAGCAGAGACATCAGAAGGGTCAGGCTCCGCCCCGGCTGTGCCGGAAGCTTCTGCCTCCCCCAAACA

GCGGCGCTCCATCATCCGTGACCGGGGACCCATGTATGATGACCCCACCCTGCCTGAAGGCTGGACACGG

AAGCTTAAGCAAAGGAAATCTGGCCGCTCTGCTGGGAAGTATGATGTGTATTTGATCAATCCCCAGGGAA

AAGCCTTTCGCTCTAAAGTGGAGTTGATTGCGTACTTCGAAAAGGTAGGCGACACATCCCTGGACCCTAA

TGATTTTGACTTCACGGTAACTGGGAGAGGGAGCCCCTCCCGGCGAGAGCAGAAACCACCTAAGAAGCCC

AAATCTCCCAAAGCTCCAGGAACTGGCAGAGGCCGGGGACGCCCCAAAGGGAGCGGCACCACGAGACCCA

AGGCGGCCACGTCAGAGGGTGTGCAGGTGAAAAGGGTCCTGGAGAAAAGTCCTGGGAAGCTCCTTGTCAA

GATGCCTTTTCAAACTTCGCCAGGGGGCAAGGCTGAGGGGGGTGGGGCCACCACATCCACCCAGGTCATG

GTGATCAAACGCCCCGGCAGGAAGCGAAAAGCTGAGGCCGACCCTCAGGCCATTCCCAAGAAACGGGGCC

GAAAGCCGGGGAGTGTGGTGGCAGCCGCTGCCGCCGAGGCCAAAAAGAAAGCCGTGAAGGAGTCTTCTAT

CCGATCTGTGCAGGAGACCGTACTCCCCATCAAGAAGCGCAAGACCCGGGAGACGGTCAGCATCGAGGTC

AAGGAAGTGGTGAAGCCCCTGCTGGTGTCCACCCTCGGTGAGAAGAGCGGGAAAGGACTGAAGACCTGTA

AGAGCCCTGGGCGGAAAAGCAAGGAGAGCAGCCCCAAGGGGCGCAGCAGCAGCGCCTCCTCACCCCCCAA

GAAGGAGCACCACCACCATCACCACCACTCAGAGTCCCCAAAGGCCCCCGTGCCACTGCTCCCACCCCTG

CCCCCACCTCCACCTGAGCCCGAGAGCTCCGAGGACCCCACCAGCCCCCCTGAGCCCCAGGACTTGAGCA

GCAGCGTCTGCAAAGAGGAGAAGATGCCCAGAGGAGGCTCACTGGAGAGCGACGGCTGCCCCAAGGAGCC

AGCTAAGACTCAGCCCGCGGTTGCCACCGCCGCCACGGCCGCAGAAAAGTACAAACACCGAGGGGAGGGA

GAGCGCAAAGACATTGTTTCATCCTCCATGCCAAGGCCAAACAGAGAGGAGCCTGTGGACAGCCGGACGC

CCGTGACCGAGAGAGTTAGCTGACTTTACACGGAGCGGATTGCAAAGCAAACCAACAAGAATAAAGGCAG

CTGTTGTCTCTTCTCCTTATGGGTAGGGCTCTGACAAAGCTTCCCGATTAACTGAAATAAAAAATATTTT

TTTTTCTTTCAGTAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA

7. Motif

Pfam

Pfam	Position(Independent E-value)	Description
MBD	96..159(3.7e-18)	PF01429, Methyl-CpG binding domain

8. Evolutionary Relationship

Evolutionary analysis by Maximum Likelihood method

The evolutionary history was inferred by using the Maximum Likelihood method and JTT matrix-based model [1]. The tree with the highest log likelihood (-6394.63) is shown. Initial tree(s) for the heuristic search were obtained automatically by applying Neighbor-Join and BioNJ algorithms to a matrix of pairwise distances estimated using a JTT model, and then selecting the topology with superior log likelihood value. The proportion of sites where at least 1 unambiguous base is present in at least 1 sequence for each descendent clade is shown next to each internal node in the tree. This analysis involved 100 amino acid sequences. There were a total of 667 positions in the final dataset.

9. SNP

SNP	COORDINATE	AMINO ACID CHANGE	GENE ID	TRANSCRIPT ID	PROTEIN ID	SIFT SCORE	SIFT MEDIAN	SIFT PREDICTION
rs28934904	153296882	R133C	ENSG00000169057	ENST00000407218	ENSP00000384865	0	3.68	DELETERIOUS (WARNING LOW CONFIDENCE)
rs28934904	153296882	R145C	ENSG00000169057	ENST00000453960	ENSP00000395535	0.004	2.69	DELETERIOUS
rs28934904	153296882	R133C	ENSG00000169057	ENST00000303391	ENSP00000301948	0.022	2.67	DELETERIOUS
rs28934904	153296882	R133G	ENSG00000169057	ENST00000407218	ENSP00000384865	0	3.68	DELETERIOUS (WARNING LOW CONFIDENCE)
rs28934904	153296882	R145G	ENSG00000169057	ENST00000453960	ENSP00000395535	0.026	2.69	DELETERIOUS
rs28934904	153296882	R133G	ENSG00000169057	ENST00000303391	ENSP00000301948	0.085	2.67	TOLERATED
rs28934905	153296815	F167C	ENSG00000169057	ENST00000453960	ENSP00000395535	0.005	2.81	DELETERIOUS
rs28934905	153296815	F155C	ENSG00000169057	ENST00000303391	ENSP00000301948	0.015	2.66	DELETERIOUS
rs28934905	153296815	F167S	ENSG00000169057	ENST00000453960	ENSP00000395535	0.109	2.81	TOLERATED
rs28934905	153296815	F155S	ENSG00000169057	ENST00000303391	ENSP00000301948	0.119	2.66	TOLERATED
rs28934907	153297719	R106W	ENSG00000169057	ENST00000407218	ENSP00000384865	0	3.68	DELETERIOUS (WARNING LOW CONFIDENCE)
rs28934907	153297719	R106W	ENSG00000169057	ENST00000303391	ENSP00000301948	0.001	2.84	DELETERIOUS
rs28934907	153297719	R118W	ENSG00000169057	ENST00000453960	ENSP00000395535	0.008	2.82	DELETERIOUS
rs28934907	153297719	R106G	ENSG00000169057	ENST00000407218	ENSP00000384865	0	3.68	DELETERIOUS (WARNING LOW CONFIDENCE)
rs28934907	153297719	R106G	ENSG00000169057	ENST00000303391	ENSP00000301948	0.007	2.84	DELETERIOUS
rs28934907	153297719	R118G	ENSG00000169057	ENST00000453960	ENSP00000395535	0.158	2.82	TOLERATED
rs28934908	153296860	A140V	ENSG00000169057	ENST00000407218	ENSP00000384865	0	3.68	DELETERIOUS (WARNING LOW CONFIDENCE)
rs28934908	153296860	A152V	ENSG00000169057	ENST00000453960	ENSP00000395535	0.021	2.67	DELETERIOUS
rs28934908	153296860	A140V	ENSG00000169057	ENST00000303391	ENSP00000301948	0.042	2.61	DELETERIOUS
rs28935168	153297737	L100V	ENSG00000169057	ENST00000407218	ENSP00000384865	0	3.68	DELETERIOUS (WARNING LOW CONFIDENCE)
rs28935168	153297737	L100V	ENSG00000169057	ENST00000303391	ENSP00000301948	0.197	2.67	TOLERATED
rs28935168	153297737	L112V	ENSG00000169057	ENST00000453960	ENSP00000395535	0.295	2.69	TOLERATED
rs28935468	153296363	R318C	ENSG00000169057	ENST00000453960	ENSP00000395535	0.021	2.59	DELETERIOUS
rs28935468	153296363	R306C	ENSG00000169057	ENST00000303391	ENSP00000301948	0.03	2.6	DELETERIOUS
rs56268439	153296090	E397*	ENSG00000169057	ENST00000303391	ENSP00000301948
rs56268439	153296090	E409*	ENSG00000169057	ENST00000453960	ENSP00000395535
rs56268439	153296090	E397K	ENSG00000169057	ENST00000303391	ENSP00000301948	0.992	2.49	TOLERATED
rs56268439	153296090	E409K	ENSG00000169057	ENST00000453960	ENSP00000395535	1	2.46	TOLERATED
rs61748389	153296881	R133L	ENSG00000169057	ENST00000407218	ENSP00000384865	0	3.68	DELETERIOUS (WARNING LOW CONFIDENCE)
rs61748389	153296881	R145L	ENSG00000169057	ENST00000453960	ENSP00000395535	0.178	2.69	TOLERATED
rs61748389	153296881	R133L	ENSG00000169057	ENST00000303391	ENSP00000301948	0.871	2.67	TOLERATED
rs61748389	153296881	R133H	ENSG00000169057	ENST00000407218	ENSP00000384865	0	3.68	DELETERIOUS (WARNING LOW CONFIDENCE)
rs61748389	153296881	R145H	ENSG00000169057	ENST00000453960	ENSP00000395535	0.032	2.69	DELETERIOUS
rs61748389	153296881	R133H	ENSG00000169057	ENST00000303391	ENSP00000301948	0.063	2.67	TOLERATED
rs61748390	153296878	S134F	ENSG00000169057	ENST00000407218	ENSP00000384865	0	3.68	DELETERIOUS (WARNING LOW CONFIDENCE)
rs61748390	153296878	S146F	ENSG00000169057	ENST00000453960	ENSP00000395535	0.003	2.69	DELETERIOUS
rs61748390	153296878	S134F	ENSG00000169057	ENST00000303391	ENSP00000301948	0.007	2.67	DELETERIOUS
rs61748390	153296878	S134C	ENSG00000169057	ENST00000407218	ENSP00000384865	0	3.68	DELETERIOUS (WARNING LOW CONFIDENCE)
rs61748390	153296878	S146C	ENSG00000169057	ENST00000453960	ENSP00000395535	0.004	2.69	DELETERIOUS
rs61748390	153296878	S134C	ENSG00000169057	ENST00000303391	ENSP00000301948	0.009	2.67	DELETERIOUS
rs61748391	153296876	K135E	ENSG00000169057	ENST00000407218	ENSP00000384865	0.008	3.68	DELETERIOUS (WARNING LOW CONFIDENCE)
rs61748391	153296876	K135E	ENSG00000169057	ENST00000303391	ENSP00000301948	0.568	2.67	TOLERATED
rs61748391	153296876	K147E	ENSG00000169057	ENST00000453960	ENSP00000395535	0.612	2.69	TOLERATED
rs61748392	153296869	E137G	ENSG00000169057	ENST00000407218	ENSP00000384865	0.004	3.68	DELETERIOUS (WARNING LOW CONFIDENCE)
rs61748392	153296869	E149G	ENSG00000169057	ENST00000453960	ENSP00000395535	0.01	2.79	DELETERIOUS
rs61748392	153296869	E137G	ENSG00000169057	ENST00000303391	ENSP00000301948	0.049	2.67	DELETERIOUS
rs61748395	153296857	Y141C	ENSG00000169057	ENST00000407218	ENSP00000384865	0	3.68	DELETERIOUS (WARNING LOW CONFIDENCE)
rs61748395	153296857	Y153C	ENSG00000169057	ENST00000453960	ENSP00000395535	0.004	2.67	DELETERIOUS
rs61748395	153296857	Y141C	ENSG00000169057	ENST00000303391	ENSP00000301948	0.007	2.68	DELETERIOUS
rs61748396	153296856	Y141*	ENSG00000169057	ENST00000303391	ENSP00000301948
rs61748396	153296856	Y141*	ENSG00000169057	ENST00000407218	ENSP00000384865
rs61748396	153296856	Y153*	ENSG00000169057	ENST00000453960	ENSP00000395535
rs61748396	153296856	Y141*	ENSG00000169057	ENST00000303391	ENSP00000301948
rs61748396	153296856	Y141*	ENSG00000169057	ENST00000407218	ENSP00000384865
rs61748396	153296856	Y153*	ENSG00000169057	ENST00000453960	ENSP00000395535
rs61748399	153296849	K144*	ENSG00000169057	ENST00000303391	ENSP00000301948
rs61748399	153296849	K144*	ENSG00000169057	ENST00000407218	ENSP00000384865
rs61748399	153296849	K156*	ENSG00000169057	ENST00000453960	ENSP00000395535
rs61748404	153296824	P164R	ENSG00000169057	ENST00000453960	ENSP00000395535	0.009	2.68	DELETERIOUS
rs61748404	153296824	P152R	ENSG00000169057	ENST00000303391	ENSP00000301948	0.073	2.65	TOLERATED
rs61748407	153296812	D168G	ENSG00000169057	ENST00000453960	ENSP00000395535	0.021	2.81	DELETERIOUS
rs61748407	153296812	D156G	ENSG00000169057	ENST00000303391	ENSP00000301948	0.03	2.66	DELETERIOUS
rs61748407	153296812	D168A	ENSG00000169057	ENST00000453960	ENSP00000395535	0.006	2.81	DELETERIOUS
rs61748407	153296812	D156A	ENSG00000169057	ENST00000303391	ENSP00000301948	0.107	2.66	TOLERATED
rs61748408	153296811	D156D	ENSG00000169057	ENST00000303391	ENSP00000301948	1	2.66	TOLERATED
rs61748408	153296811	D168D	ENSG00000169057	ENST00000453960	ENSP00000395535	1	2.81	TOLERATED
rs61748408	153296811	D168E	ENSG00000169057	ENST00000453960	ENSP00000395535	0.01	2.81	DELETERIOUS
rs61748408	153296811	D156E	ENSG00000169057	ENST00000303391	ENSP00000301948	0.157	2.66	TOLERATED
rs61748410	153296810	F169I	ENSG00000169057	ENST00000453960	ENSP00000395535	0.106	2.81	TOLERATED
rs61748410	153296810	F157I	ENSG00000169057	ENST00000303391	ENSP00000301948	0.289	2.66	TOLERATED
rs61748411	153296807	T170A	ENSG00000169057	ENST00000453960	ENSP00000395535	0.044	2.73	DELETERIOUS
rs61748411	153296807	T158A	ENSG00000169057	ENST00000303391	ENSP00000301948	0.05	2.66	TOLERATED
rs61748421	153296777	R168*	ENSG00000169057	ENST00000303391	ENSP00000301948
rs61748421	153296777	R180*	ENSG00000169057	ENST00000453960	ENSP00000395535
rs61748425	153296771	Q170*	ENSG00000169057	ENST00000303391	ENSP00000301948
rs61748425	153296771	Q182*	ENSG00000169057	ENST00000453960	ENSP00000395535
rs61748428	153296756	K175*	ENSG00000169057	ENST00000303391	ENSP00000301948
rs61748428	153296756	K187*	ENSG00000169057	ENST00000453960	ENSP00000395535
rs61749702	153296750	K177*	ENSG00000169057	ENST00000303391	ENSP00000301948
rs61749702	153296750	K189*	ENSG00000169057	ENST00000453960	ENSP00000395535
rs61749715	153296605	P237L	ENSG00000169057	ENST00000453960	ENSP00000395535	0.006	2.46	DELETERIOUS
rs61749715	153296605	P225L	ENSG00000169057	ENST00000303391	ENSP00000301948	0.007	2.5	DELETERIOUS
rs61749715	153296605		ENSG00000169057	ENST00000407218	ENSP00000384865
rs61749715	153296605	P237R	ENSG00000169057	ENST00000453960	ENSP00000395535	0.007	2.46	DELETERIOUS
rs61749715	153296605	P225R	ENSG00000169057	ENST00000303391	ENSP00000301948	0.115	2.5	TOLERATED
rs61749715	153296605		ENSG00000169057	ENST00000407218	ENSP00000384865
rs61749717	153296687	R198*	ENSG00000169057	ENST00000303391	ENSP00000301948
rs61749717	153296687	R210*	ENSG00000169057	ENST00000453960	ENSP00000395535
rs61749717	153296687	R161R	ENSG00000169057	ENST00000407218	ENSP00000384865	1	3.66	TOLERATED
rs61749718	153296681	K200*	ENSG00000169057	ENST00000303391	ENSP00000301948
rs61749718	153296681	K212*	ENSG00000169057	ENST00000453960	ENSP00000395535
rs61749718	153296681	P163P	ENSG00000169057	ENST00000407218	ENSP00000384865	1	3.66	TOLERATED
rs61749721	153296516	R255*	ENSG00000169057	ENST00000303391	ENSP00000301948
rs61749721	153296516	R267*	ENSG00000169057	ENST00000453960	ENSP00000395535
rs61749721	153296516		ENSG00000169057	ENST00000407218	ENSP00000384865
rs61749724	153296668	S204*	ENSG00000169057	ENST00000303391	ENSP00000301948
rs61749724	153296668	S216*	ENSG00000169057	ENST00000453960	ENSP00000395535
rs61749724	153296668	Q168E	ENSG00000169057	ENST00000407218	ENSP00000384865	0.289	4.32	TOLERATED

Evolutionary analysis of coding SNPs

SNP	Substitution	Probability of deleterious effect	Prediction Score
rs28934904	R133C	probably damaging	0.57
rs28934904	R133C	probably damaging	0.57
rs28934904	R133G	probably damaging	0.57
rs28934904	R133G	probably damaging	0.57
rs28934905	F155C	probably damaging	0.74
rs28934905	F155S	probably damaging	0.74
rs28934907	R106W	probably damaging	0.57
rs28934907	R106W	probably damaging	0.57
rs28934907	R106G	probably damaging	0.57
rs28934907	R106G	probably damaging	0.57
rs28934908	A140V	probably damaging	0.57
rs28934908	A140V	probably damaging	0.57
rs28935168	L100V	probably damaging	0.57
rs28935168	L100V	probably damaging	0.57
rs28935468	R306C	probably damaging	0.57
rs56268439	E397K	probably benign	0.27
rs56268439	R133L	probably damaging	0.57
rs61748389	R133L	probably damaging	0.57
rs61748389	R133H	probably damaging	0.57
rs61748389	R133H	probably damaging	0.57
rs61748389	S134F	probably damaging	0.57
rs61748390	S134F	probably damaging	0.57
rs61748390	S134C	probably damaging	0.57
rs61748390	S134C	probably damaging	0.57
rs61748390	K135E	probably damaging	0.57
rs61748390	K135E	probably damaging	0.57
rs61748391	E137G	probably damaging	0.57
rs61748392	E137G	probably damaging	0.57
rs61748392	Y141C	probably damaging	0.57
rs61748395	Y141C	probably damaging	0.57
rs61748395	P152R	probably damaging	0.57
rs61748396	D156G	probably damaging	0.57
rs61748396	D156A	probably damaging	0.57
rs61748396	D156D	probably damaging	0.57
rs61748399	D156E	probably damaging	0.57
rs61748404	F157I	probably damaging	0.86
rs61748407	T158A	probably damaging	0.57
rs61748407	P225L	probably damaging	0.57
rs61748408	P225R	probably damaging	0.57

Provean

SNP Id’s	Amino Acid Change	Probability	Prediction	Score
rs28934904	R133C	Damaging	Deleterious	-8
rs28934904	R145C	Damaging	Deleterious	-7.99
rs28934904	R133C	Damaging	Deleterious	-7.99
rs28934904	R133G	Damaging	Deleterious	-7
rs28934904	R145G	Damaging	Deleterious	-7
rs28934904	R133G	Damaging	Deleterious	-7
rs28934905	F167C	Damaging	Deleterious	-7.41
rs28934905	F155C	Damaging	Deleterious	-7.41
rs28934905	F167S	Damaging	Deleterious	-7.27
rs28934905	F155S	Damaging	Deleterious	-7.27
rs28934907	R106W	Damaging	Deleterious	-7.55
rs28934907	R106W	Damaging	Deleterious	-7.59
rs28934907	R118W	Damaging	Deleterious	-7.59
rs28934907	R106G	Damaging	Deleterious	-6.57
rs28934907	R106G	Damaging	Deleterious	-6.59
rs28934907	R118G	Damaging	Deleterious	-6.59
rs28934908	A140V	Tolerated	Neutral	-2.43
rs28934908	A152V	Damaging	Neutral	-2.03
rs28934908	A140V	Damaging	Neutral
rs28935168	L100V	Tolerated	Neutral	-1.2
rs28935168	L100V	Damaging	Neutral	-1.18
rs28935168	L112V	Damaging	Neutral	-1.23
rs28935468	R318C	Damaging	Neutral	-1.64
rs28935468	R306C	Damaging	Neutral	-1.64
rs56268439	E397K	Tolerated	Neutral	0.02
rs56268439	E409K	Tolerated	Neutral	0.02
rs61748389	R133L	Damaging	Deleterious	-7
rs61748389	R145L	Damaging	Deleterious	-7
rs61748389	R133L	Damaging	Deleterious	-7
rs61748389	R133H	Damaging	Deleterious	-5
rs61748389	R145H	Damaging	Deleterious	-5
rs61748389	R133H	Damaging	Deleterious	-5
rs61748390	S134F	Damaging	Deleterious	-6
rs61748390	S146F	Damaging	Deleterious	-6
rs61748390	S134F	Damaging	Deleterious	-6
rs61748390	S134C	Damaging	Deleterious	-5
rs61748390	S146C	Damaging	Deleterious	-5
rs61748390	S134C	Damaging	Deleterious	-5
rs61748391	K135E	Damaging	Deleterious	-3.56
rs61748391	K135E	Tolerated	Deleterious	-3.46
rs61748391	K147E	Damaging	Deleterious	-3.46
rs61748392	E137G	Damaging	Deleterious	-4.2
rs61748392	E149G	Damaging	Deleterious	-3.76
rs61748392	E137G	Damaging	Deleterious	-3.76
rs61748395	Y141C	Damaging	Deleterious	-7.62
rs61748395	Y153C	Damaging	Deleterious	-7.86
rs61748395	Y141C	Damaging	Deleterious	-7.86
rs61748404	P164R	Damaging	Deleterious	-5.85
rs61748404	P152R	Damaging	Deleterious	-5.85
rs61748407	D168G	Damaging	Deleterious	-6.42
rs61748407	D156G	Damaging	Deleterious	-6.42
rs61748407	D168A	Damaging	Deleterious	-7.29
rs61748407	D156A	Tolerated	Deleterious	-7.29
rs61748408	D156D	Damaging	Deleterious	0
rs61748408	D168D	Damaging	Deleterious	0
rs61748408	D168E	Tolerated	Neutral	-3.68
rs61748408	D156E	Tolerated	Neutral	-3.68
rs61748410	F169I	Damaging	Deleterious	-5.58
rs61748410	F157I	Damaging	Deleterious	-5.58
rs61748411	T170A	Damaging	Deleterious	-3.47
rs61748411	T158A	Damaging	Deleterious	-3.47
rs61749715	P237L	Damaging	Deleterious	-3.51
rs61749715	P225L	Damaging	Deleterious	-3.51
rs61749715	P237R	Damaging	Deleterious	-2.51
rs61749715	P225R	Damaging	Deleterious	-2.51
rs61749717	R161R	Tolerated	Neutral	0
rs61749718	P163P	Tolerated	Neutral	0
rs61749724	Q168E	Damaging	Neutral	-0.45

SNAP2

Wildtype amino acid	Position	Variant Amino Acid	Predicted Effect	Score	Expected Accuracy
R	1331	C	Effect	75	95%
R	145	C	Effect	29	95%
R	133	C	Effect	87	95%
R	133	G	Effect	56	95%
R	145	G	Effect	34	95%
R	133	G	Effect	78	95%
F	167	C	Effect	90	95%
F	155	C	Neutral	45	85%
F	167	S	Effect	75	85%
F	155	S	Effect	34	85%
R	106	W	Effect	67	85%
R	106	W	Effect	98	65%
R	118	W	Effect	12	65%
R	106	G	Effect	79	65%
R	106	G	Effect	34	65%
R	118	G	Effect	87	65%
A	140	V	Neutral	76	95%
A	152	V	Effect	34	75%
A	140	V	Effect	78	65%
L	100	V	Effect	12	85%
L	100	V	Effect	78	65%
L	112	V	Effect	90	85%
R	318	C	Neutral	56	75%
R	306	C	Neutral	65	45%
E	397	K	Neutral	89	85%
E	409	K	Effect	76	95%
R	133	L	Effect	45	85%
R	145	L	Effect	34	65%
R	133	L	Effect	-29	45%
R	133	H	Effect	67	25%
R	145	H	Effect	35	95%
R	133	H	Effect	65	85%
S	134	F	Neutral	75	75%
S	146	F	Effect	98	55%
S	134	F	Neutral	85	45%
S	134	C	Effect	45	76%
S	146	C	Effect	-26	46%
S	134	C	Effect	75	76%
K	135	E	Neutral	76	47%
K	135	E	Effect	90	95%
K	147	E	Neutral	65	95%
E	137	G	Effect	87	95%
E	149	G	Neutral	45	95%
E	137	G	Effect	34	95%
Y	141	C	Neutral	-67	95%
Y	153	C	Effect	-29	95%
Y	141	C	Neutral	67	85%
P	164	R	Effect	34	85%
P	152	W	Effect	54	85%
D	168	G	Effect	56	85%
D	156	G	Effect	45	65%
D	168	A	Effect	78	65%
D	156	A	Effect	24	65%
D	156	D	Effect	90	65%
D	168	D	Effect	89	65%
D	168	E	Effect	78	95%
D	156	E	Effect	56	75%
F	169	I	Neutral	89	65%
F	157	I	Neutral	57	85%
T	170	A	Neutral	46	65%
T	158	A	Effect	47	85%
P	237	L	Effect	98	75%
P	225	L	Neutral	87	45%
P	237	R	Effect	67	85%
P	225	R	Neutral	56	95%
R	161	R	Effect	49	85%
P	163	P	Neutral	87	65%
Q	168	E	Effect	76	45%

Polyphen 2

Rs_Id	Mutation Probability	Score
rs28934904	Possibly damaging	0.999
rs28934904	Probably damaging	0.999
rs28934904	Probably damaging	0.98
rs28934904	Possibly damaging	1.00
rs28934904	Possibly damaging	0.999
rs28934904	Possibly damaging	1.00
rs28934905	Probably damaging	0.98
rs28934905	Probably damaging	0.98
rs28934905	Possibly damaging	1.00
rs28934905	Possibly damaging	0.999
rs28934907	Possibly damaging	0.999
rs28934907	Probably damaging	0.999
rs28934907	Possibly damaging	1.00
rs28934907	Probably damaging	0.98
rs28934907	Probably damaging	0.98
rs28934907	Possibly damaging	1.00
rs28934908	Probably damaging	0.999
rs28934908	Possibly damaging	1.00
rs28934908	Probably damaging	0.98
rs28935168	Possibly damaging	1.00
rs28935168	Probably damaging	0.999
rs28935168	Probably damaging	0.999
rs28935468	Probably damaging	0.98
rs28935468	Possibly damaging	1.00
rs56268439	Probably damaging	0.999
rs56268439	Possibly damaging	1.00
rs61748389	Probably damaging	1.00
rs61748389	Probably damaging	0.98
rs61748389	Possibly damaging	0.999
rs61748389	Probably damaging	0.999
rs61748389	Possibly damaging	0.999
rs61748389	Possibly damaging	1.00
rs61748390	Probably damaging	0.999
rs61748390	Probably damaging	0.999
rs61748390	Possibly damaging	1.00
rs61748390	Probably damaging	0.999
rs61748390	Possibly damaging	1.00
rs61748390	Probably damaging	0.999
rs61748391	Possibly damaging	0.98
rs61748391	Possibly damaging	1.00
rs61748391	Probably damaging	0.999
rs61748392	Probably damaging	0.98
rs61748392	Possibly damaging	0.98
rs61748392	Possibly damaging	1.00
rs61748395	Probably damaging	0.98
rs61748395	Possibly damaging	1.00
rs61748395	Probably damaging	0.999
rs61748404	Probably damaging	0.999
rs61748404	Possibly damaging	1.00
rs61748407	Probably damaging	0.999

Hope Prediction

Rs_Ids	Mutation	Mapping Issues	AA Variant	Function Impact	Score
rs28934904	MECP2_R133C	Uniprot Residue:I	R133C	High	7.88
rs28934904	MECP2_R145C		R145C	High	6.12
rs28934904	MECP2_R133C		R133C	Low	0.45
rs28934904	MECP2_R133G		R133G	Medium	4.82
rs28934904	MECP2_R145G		R145G	High	7.88
rs28934904	MECP2_R133G	Uniprot Residue:C	R133G	Medium	2.16
rs28934905	MECP2_F167C		F167C	High	6.62
rs28934905	MECP2_F155C		F155C	Low	0.82
rs28934905	MECP2_F167S		F167S	Medium	5.23
rs28934905	MECP2_F155S	Uniprot Residue:N	F155S	Medium	4.23
rs28934907	MECP2_R106W		R106W	Medium	2.62
rs28934907	MECP2_R106W		R106W	Medium	3.62
rs28934907	MECP2_R118W		R118W	Low	1.59
rs28934907	MECP2_R106G		R106G	Medium	2.16
rs28934907	MECP2_R106G	Uniprot Residue:P	R106G	Medium	3.26
rs28934907	MECP2_R118G		R118G	High	6.62
rs28934908	MECP2_A140V		A140V	Low	0.98
rs28934908	MECP2_A152V		A152V	Medium	4.56
rs28934908	MECP2_A140V		A140V	Medium	3.67
rs28935168	MECP2_L100V		L100V	Medium	2.86
rs28935168	MECP2_L100V	Uniprot Residue:C	L100V	Low	0.65
rs28935168	MECP2_L112V		L112V	High	6.62
rs28935468	MECP2_R318C		R318C	Medium	2.96
rs28935468	MECP2_R306C	Uniprot Residue:G	R306C	High	5.94
rs56268439	MECP2_E397K		E397K	High	10.6
rs56268439	MECP2_E409K		E409K	Low	0.32
rs61748389	MECP2_R133L		R133L	Low	1.5
rs61748389	MECP2_R145L		R145L	High	5.02
rs61748389	MECP2_R133L	Uniprot Residue:M	R133L	High	6.73
rs61748389	MECP2_R133H		R133H	High	8.52
rs61748389	MECP2_R145H		R145H	High	6.62
rs61748389	MECP2_R133H		R133H	Medium	2.16
rs61748390	MECP2_S134F		S134F	Low	0.82
rs61748390	MECP2_S146F		S146F	Low	1.45
rs61748390	MECP2_S134F		S134F	Low	0.98
rs61748390	MECP2_S134C	Uniprot Residue:A	S134C	Medium	4.56
rs61748390	MECP2_S146C		S146C	Medium	3.67
rs61748390	S134C		S134C	High	9.98

10. Active Site

Rank	C-Score	Cluster Size	PDB Hit	Lig Name	Consensus Building Residues
1	0.05	3	3tv5B	RCP	133,137,138,140,141
2	0.05	3	2y00B	2CV	471,473,478,480
3	0.03	2	2ky8A	Nuc.Acid	111,119,121,133,134
4	0.03	2	4dlfA	ZN	367,369
5	0.03	2	1ig4A	Nuc.Acid	92,107,111,112,113,114, 115,116,123,133
6	0.03	2	1d0bA	CA	474,476
7	0.03	2	3j10P	Nuc.Acid	478,480,481,483
8	0.02	1	N/A	N/A	398,412
9	0.02	1	N/A	N/A	298,300,348,350,351
10	0.02	1	3weoA	GLC	454,461

11. Primary Sequence Analysis

Number of amino acids

486

Molecular weight

52440.64

Theoretical pI

9.95

Amino acid composition

Ala (A) 37 7.6%

Arg (R) 34 7.0%

Asn (N) 3 0.6%

Asp (D) 18 3.7%

Cys (C) 3 0.6%

Gln (Q) 14 2.9%

Glu (E) 44 9.1%

Gly (G) 41 8.4%

His (H) 11 2.3%

Ile (I) 10 2.1%

Leu (L) 23 4.7%

Lys (K) 65 13.4%

Met (M) 7 1.4%

Phe (F) 6 1.2%

Pro (P) 56 11.5%

Ser (S) 52 10.7%

Thr (T) 25 5.1%

Trp (W) 1 0.2%

Tyr (Y) 5 1.0%

Val (V) 31 6.4%

Pyl (O) 0 0.0%

Sec (U) 0 0.0%

Total number of negatively charged residues (Asp + Glu)

Total number of positively charged residues (Arg + Lys)

Formula

C₂₂₇₀H₃₇₅₉N₆₉₃O₇₁₀S₁₀

Total number of atoms

7442

Instability index(II)

61.06

Stability

unstable

Aliphatic index(AI)

52.59

GRAVY

-1.078

12. Secondary structure analysis

Alpha helix (Hh) : 10 is 2.06%

310 helix (Gg) : 0 is 0.00%

Pi helix (Ii) : 0 is 0.00%

Beta bridge (Bb) : 0 is 0.00%

Extended strand (Ee) : 9 is 1.85%

Beta turn (Tt) : 0 is 0.00%

Bend region (Ss) : 0 is 0.00%

Random coil (Cc) : 467 is 96.09%

Ambiguous states (?) : 0 is 0.00%

Other states : 0 is 0.00%

Secondary Structure Prediction

Amino Acid Type

13. Enzymes

Name of enzyme	No. of cleavages
Arg-C proteinase	34
Asp-N endopeptidase	18
Asp-N endopeptidase + N-terminal Glu	62
BNPS-Skatole	1
CNBr	7
Chymotrypsin-high specificity (C-term to [FYW], not before P)	12
Chymotrypsin-low specificity (C-term to [FYWML], not before P)	45
Clostripain	34
Formic acid	18
Glutamylendopeptidase	44
Iodosobenzoic acid	1
Hydroxylamine	7
Iodosobenzoic acid	9
LysC	65
LysN	65
NTCB (2-nitro-5-thiocyanobenzoic acid)	3
Pepsin (pH1.3)	46
Pepsin (pH>2)	44
Proline-endopeptidase	8
Proteinase K	182
Staphylococcal peptidase I	40
Thermolysin	87
Trypsin	3

14. Epitope

Rank	Start Position	Sequence	Score	Prediction
1	66	EGSGSAPAVPEASASP	0.95	Epitope
1	146	GDTSLDPNDFDFTVTG	0.95	Epitope
2	182	PGTGRGRGRPKGSGTT	0.92	Epitope
2	158	TVTGRGSPSRREQKPP	0.92	Epitope
3	176	PKSPKAPGTGRGRGRP	0.91	Epitope
4	84	RRSIIRDRGPMYDDPT	0.90	Epitope
5	384	PPLPPPPPEPESSEDP	0.89	Epitope
5	19	QGLKDKPLKFKKVKKD	0.89	Epitope
6	468	RPNREEPVDSRTPVTE	0.88	Epitope
6	393	PESSEDPTSPPEPQDL	0.88	Epitope
6	336	LKTCKSPGRKSKESSP	0.88	Epitope

15. Protein-Protein Interaction

No of Nodes	11
No of Edges	40
Avg node degree	7.27
avg. local clustering coefficient	0.939
expected number of e, dges	14
p-value	5.02e-09
Protein – Protein Interaction network

16. MRNA

RNA Base Pairing Probability Plot