IGDRPT (Indian Genetic Disease Risk Prediction Tool)

Disease Name: Costello Syndrome

1 .Inheritance

Autosomal Dominant

2. Gene Name

HRAS

3. Protein Name

GTPase HRas

4. Chromosomal Location

11p15.5

5. Protein Sequence

>sp|P01112|RASH_HUMAN GTPaseHRas OS=Homo sapiens OX=9606 GN=HRAS PE=1 SV=1

MTEYKLVVVGAGGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAG

QEEYSAMRDQYMRTGEGFLCVFAINNTKSFEDIHQYREQIKRVKDSDDVPMVLVGNKCDL

AARTVESRQAQDLARSYGIPYIETSAKTRQGVEDAFYTLVREIRQHKLRKLNPPDESGPG

CMSCKCVLS

6. Gene Sequence

>NC_000011.9:c537287-532242 Homo sapiens chromosome 11, GRCh37.p13 Primary Assembly

GCAGGCGCGTCAGGTGCCAGCTTCCTGCGGCTCCGTGCCTGGGCCGTCGCGATGCACGTGTCGCGTTTCC

TCGCGATCCTGGCGCTTCCCACGCGGGGCGGGTAAAGGCGGTCTCTGCTGGAGGCTCGCGCCCACCTTTC

CCAGGTGGAAGGGTCGCCCCTGGGGCCGAGGCCTGCCGTCCTGACCTTCGGTTGGAAGTGAGGCCGACGG

CAAAAGGAAGCACCGGGGGAAGCGCCCCCGAGGACCAGGAAACACACACCGGACGCCGGAGCGCACCCGA

GTGCCCGGCCCGCGGGACACGCTGCCGCCCGCCGTCCAGTCGCCGCTTCTCACTCGCGTTCATGCGTGTC

CGCCCCGAGCCGAGCTCTGACTGCGACCGCGCGGTGGACGGACGGCAGGCGGGACCCCCGGGACCGCACG

TGGGTGGAGCCCCGGGTCAGCAGCGACCGGCGCAGGAGGGCGAGGCGGGCGCTGGACTGGGCAGAGGCAG

GGTTTGCCTGACTGTAAAACGCCTTTTTTGTTTTGAGACGAAGTAGCGCTCTGTTGCCCAGTGCAGTGGC

GCGATTTCGGCTCACCGCAACATCCGCCTCCCGGGTTCCAGCGATTCTCCTGCCTCAGCCTCCCGAGTAG

CTGGGACTACAGGCGCGCGCCACTGCAGCCGACTAATTTTTTGTGTTTTTAGTAGAGACAGGGTTTCATC

ATGTTGGCCAGGCTGGTCTTGAACTCCTGACCTCAAGTAATCCACCCGCTTAGGCCTCCCGAAGTGCTGG

GATTATAGGCGTGAGCCACCGCGCCCGGCCCTTTTTGTTTTTTAATGAGGATGTATTTCTGATTCCTTTG

CAATTTTAAAAAATGTTAAAAACATGTCTTTTTGGGTTTGAAAGAGCTAGGATGTGCGTCTATGTGCTTG

GGGTGAGCCCTGGGCACTTCGCTCCCCTGTGGCAACTTGTGGGTACGGTTTAACTGGACCACGCTGAGCT

TCTGCAGCGTTGGAACCTCAAGTTTGGGGGGACTGGGCGGGCAGGGTCGCCTGCCACGCAGGCCCGAGAA

AGAGGAGAGTGGTGGAGGGGGCGTTCTCACGCCTGGCCCCAGGGCACACGGCTGCGCCCGCCGCCCGGAA

CCCCACCGGGGCTGCAAGCGTCCTCGGGGTGGGTTGCGGTGGGAGTAGGGGAGCTGGGGTGCGTGGTGGT

AGGTGGGGTGCGCGGCCGCTCCACCTGCGCGGAAGGGCAGCCGGGCAACCGGACCCCGCGGCCACCCGGG

GGCCCCCAGCTCCGAGCATCCCGCCTTGGTCCCGGCGGATCCCAGCCTTTCCCCAGCCCGTAGCCCCGGG

ACCTCCGCGGTGGGCGGCGCCGCGCTGCCGGCGCAGGGAGGGCCTCTGGTGCACCGGCACCGCTGAGTCG

GGTTCTCTCGCCGGCCTGTTCCCGGGAGAGCCCGGGGCCCTGCTCGGAGATGCCGCCCCGGGCCCCCAGA

CACCGGCTCCCTGGCCTTCCTCGAGCAACCCCGAGCTCGGCTCCGGTCTCCAGCCAAGCCCAACCCCGAG

AGGCCGCGGCCCTACTGGCTCCGCCTCCCGCGTTGCTCCCGGAAGCCCCGCCCGACCGCGGCTCCTGACA

GACGGGCCGCTCAGCCAACCGGGGTGGGGCGGGGCCCGATGGCGCGCAGCCAATGGTAGGCCGCGCCTGG

CAGACGGACGGGCGCGGGGCGGGGCGTGCGCAGGCCCGCCCGAGTCTCCGCCGCCCGTGCCCTGCGCCCG

CAACCCGAGCCGCACCCGCCGCGGACGGAGCCCATGCGCGGGGCGAACCGCGCGCCCCCGCCCCCGCCCC

GCCCCGGCCTCGGCCCCGGCCCTGGCCCCGGGGGCAGTCGCGCCTGTGAACGGTGAGTGCGGGCAGGGAT

CGGCCGGGCCGCGCGCCCTCCTCGCCCCCAGGCGGCAGCAATACGCGCGGCGCGGGCCGGGGGCGCGGGG

CCGGCGGGCGTAAGCGGCGGCGGCGGCGGCGGCGGCGGGTGGGTGGGGCCGGGCGGGGCCCGCGGGCACA

GGTGAGCGGGCGTCGGGGGCTGCGGCGGGCGGGGGCCCCTTCCTCCCTGGGGCCTGCGGGAATCCGGGCC

CCACCCGTGGCCTCGCGCTGGGCACGGTCCCCACGCCGGCGTACCCGGGAGCCTCGGGCCCGGCGCCCTC

ACACCCGGGGGCGTCTGGGAGGAGGCGGCCGCGGCCACGGCACGCCCGGGCACCCCCGATTCAGCATCAC

AGGTCGCGGACCAGGCCGGGGGCCTCAGCCCCAGTGCCTTTTCCCTCTCCGGGTCTCCCGCGCCGCTTCT

CGGCCCCTTCCTGTCGCTCAGTCCCTGCTTCCCAGGAGCTCCTCTGTCTTCTCCAGCTTTCTGTGGCTGA

AAGATGCCCCCGGTTCCCCGCCGGGGGTGCGGGGCGCTGCCCGGGTCTGCCCTCCCCTCGGCGGCGCCTA

GTACGCAGTAGGCGCTCAGCAAATACTTGTCGGAGGCACCAGCGCCGCGGGGCCTGCAGGCTGGCACTAG

CCTGCCCGGGCACGCCGTGGCGCGCTCCGCCGTGGCCAGACCTGTTCTGGAGGACGGTAACCTCAGCCCT

CGGGCGCCTCCCTTTAGCCTTTCTGCCGACCCAGCAGCTTCTAATTTGGGTGCGTGGTTGAGAGCGCTCA

GCTGTCAGCCCTGCCTTTGAGGGCTGGGTCCCTTTTCCCATCACTGGGTCATTAAGAGCAAGTGGGGGCG

AGGCGACAGCCCTCCCGCACGCTGGGTTGCAGCTGCACAGGTAGGCACGCTGCAGTCCTTGCTGCCTGGC

GTTGGGGCCCAGGGACCGCTGTGGGTTTGCCCTTCAGATGGCCCTGCCAGCAGCTGCCCTGTGGGGCCTG

GGGCTGGGCCTGGGCCTGGCTGAGCAGGGCCCTCCTTGGCAGGTGGGGCAGGAGACCCTGTAGGAGGACC

CCGGGCCGCAGGCCCCTGAGGAGCGATGACGGAATATAAGCTGGTGGTGGTGGGCGCCGGCGGTGTGGGC

AAGAGTGCGCTGACCATCCAGCTGATCCAGAACCATTTTGTGGACGAATACGACCCCACTATAGAGGTGA

GCCTGGCGCCGCCGTCCAGGTGCCAGCAGCTGCTGCGGGCGAGCCCAGGACACAGCCAGGATAGGGCTGG

CTGCAGCCCCTGGTCCCCTGCATGGTGCTGTGGCCCTGTCTCCTGCTTCCTCTAGAGGAGGGGAGTCCCT

CGTCTCAGCACCCCAGGAGAGGAGGGGGCATGAGGGGCATGAGAGGTACCAGGGAGAGGCTGGCTGTGTG

AACTCCCCCCACGGAAGGTCCTGAGGGGGTCCCTGAGCCCTGTCCTCCTGCAGGATTCCTACCGGAAGCA

GGTGGTCATTGATGGGGAGACGTGCCTGTTGGACATCCTGGATACCGCCGGCCAGGAGGAGTACAGCGCC

ATGCGGGACCAGTACATGCGCACCGGGGAGGGCTTCCTGTGTGTGTTTGCCATCAACAACACCAAGTCTT

TTGAGGACATCCACCAGTACAGGTGAACCCCGTGAGGCTGGCCCGGGAGCCCACGCCGCACAGGTGGGGC

CAGGCCGGCTGCGTCCAGGCAGGGGCCTCCTGTCCTCTCTGCGCATGTCCTGGATGCCGCTGCGCCTGCA

GCCCCCGTAGCCAGCTCTCGCTTTCCACCTCTCAGGGAGCAGATCAAACGGGTGAAGGACTCGGATGACG

TGCCCATGGTGCTGGTGGGGAACAAGTGTGACCTGGCTGCACGCACTGTGGAATCTCGGCAGGCTCAGGA

CCTCGCCCGAAGCTACGGCATCCCCTACATCGAGACCTCGGCCAAGACCCGGCAGGTGAGGCAGCTCTCC

ACCCCACAGCTAGCCAGGGACCCGCCCCGCCCCGCCCCAGCCAGGGAGCAGCACTCACTGACCCTCTCCC

TTGACACAGGGCAGCCGCTCTGGCTCTAGCTCCAGCTCCGGGACCCTCTGGGACCCCCCGGGACCCATGT

GACCCAGCGGCCCCTCGCGCTGTAAGTCTCCCGGGACGGCAGGGCAGTGAGGGAGGCGAGGGCCGGGGTC

TGGGCTCACGCCCTGCAGTCCTGGGCCGACACAGCTCCGGGGAAGGCGGAGGTCCTTGGGGAGAGCTGCC

CTGAGCCAGGCCGGAGCGGTGACCCTGGGGCCCGGCCCCTCTTGTCCCCAGAGTGTCCCACGGGCACCTG

TTGGTTCTGAGTCTTAGTGGGGCTACTGGGGACACGGGCCGTAGCTGAGTCGAGAGCTGGGTGCAGGGTG

GTCAAACCCTGGCCAGACCTGGAGTTCAGGAGGGCCCCGGGCCACCCTGACCTTTGAGGGGCTGCTGTAG

CATGATGCGGGTGGCCCTGGGCACTTCGAGATGGCCAGAGTCCAGCTTCCCGTGTGTGTGGTGGGCCTGG

GGAAGTGGCTGGTGGAGTCGGGAGCTTCGGGCCAGGCAAGGCTTGATCCCACAGCAGGGAGCCCCTCACC

CAGGCAGGCGGCCACAGGCCGGTCCCTCCTGATCCCATCCCTCCTTTCCCAGGGAGTGGAGGATGCCTTC

TACACGTTGGTGCGTGAGATCCGGCAGCACAAGCTGCGGAAGCTGAACCCTCCTGATGAGAGTGGCCCCG

GCTGCATGAGCTGCAAGTGTGTGCTCTCCTGACGCAGGTGAGGGGGACTCCCAGGGCGGCCGCCACGCCC

ACCGGATGACCCCGGCTCCCCGCCCCTGCCGGTCTCCTGGCCTGCGGTCAGCAGCCTCCCTTGTGCCCCG

CCCAGCACAAGCTCAGGACATGGAGGTGCCGGATGCAGGAAGGAGGTGCAGACGGAAGGAGGAGGAAGGA

AGGACGGAAGCAAGGAAGGAAGGAAGGGCTGCTGGAGCCCAGTCACCCCGGGACCGTGGGCCGAGGTGAC

TGCAGACCCTCCCAGGGAGGCTGTGCACAGACTGTCTTGAACATCCCAAATGCCACCGGAACCCCAGCCC

TTAGCTCCCCTCCCAGGCCTCTGTGGGCCCTTGTCGGGCACAGATGGGATCACAGTAAATTATTGGATGG

TCTTGA

7. Motif

Pfam (11 motifs)

Pfam	Position(Independent E-value)	Description
Ras	5..164(8.2e-61)	PF00071, Ras family
Roc	5..119(8.5e-22)	PF08477, Ras of Complex, Roc, domain of DAPkinase
Arf	3..162(6.2e-09)	PF00025, ADP-ribosylation factor family
GTP_EFTU	43..162(3.2e-07)	PF00009, Elongation factor Tu GTP binding domain
MMR_HSR1	6..117(1.7e-06)	PF01926, 50S ribosome-binding GTPase
RsgA_GTPase	6..26(0.75) 106..154(0.03)	PF03193, RsgA GTPase
FeoB_N	108..154(0.0024)	PF02421, Ferrous iron transport protein B
ATP_bind_1	55..132(0.13)	PF03029, Conserved hypothetical ATP binding protein
Septin	3..50(0.072)	PF00735, Septin
Ldh_1_N	5..40(0.58)	PF00056, lactate/malate dehydrogenase, NAD binding domain
AAA_16	6..29(0.36)	PF13191, AAA ATPase 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 (-7136.51) 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 1048 positions in the final dataset.

9. SNP

SNP	COORDINATE	AMINO ACID CHANGE	GENE ID	TRANSCRIPT ID	PROTEIN ID	SIFT SCORE	SIFT MEDIAN	SIFT PREDICTION
rs28933406	533875	Q61K	ENSG00000174775	ENST00000311189	ENSP00000309845	0.016	2.72	DELETERIOUS
rs28933406	533875	Q61K	ENSG00000174775	ENST00000397596	ENSP00000380723	0.016	2.72	DELETERIOUS
rs28933406	533875	Q61K	ENSG00000174775	ENST00000451590	ENSP00000407586	0.016	2.72	DELETERIOUS
rs28933406	533875	Q61K	ENSG00000174775	ENST00000397594	ENSP00000380722	0.019	2.85	DELETERIOUS
rs28933406	533875	Q61K	ENSG00000174775	ENST00000417302	ENSP00000388246	0.019	2.85	DELETERIOUS
rs104894226	534285	G13V	ENSG00000174775	ENST00000397594	ENSP00000380722	0.021	2.85	DELETERIOUS
rs104894226	534285	G13V	ENSG00000174775	ENST00000417302	ENSP00000388246	0.021	2.85	DELETERIOUS
rs104894226	534285	G13V	ENSG00000174775	ENST00000311189	ENSP00000309845	0.022	2.72	DELETERIOUS
rs104894226	534285	G13V	ENSG00000174775	ENST00000397596	ENSP00000380723	0.022	2.72	DELETERIOUS
rs104894226	534285	G13V	ENSG00000174775	ENST00000451590	ENSP00000407586	0.022	2.72	DELETERIOUS
rs104894226	534285	G13D	ENSG00000174775	ENST00000397594	ENSP00000380722	0.023	2.85	DELETERIOUS
rs104894226	534285	G13D	ENSG00000174775	ENST00000417302	ENSP00000388246	0.023	2.85	DELETERIOUS
rs104894226	534285	G13D	ENSG00000174775	ENST00000311189	ENSP00000309845	0.024	2.72	DELETERIOUS
rs104894226	534285	G13D	ENSG00000174775	ENST00000397596	ENSP00000380723	0.024	2.72	DELETERIOUS
rs104894226	534285	G13D	ENSG00000174775	ENST00000451590	ENSP00000407586	0.024	2.72	DELETERIOUS
rs104894227	533553	K117R	ENSG00000174775	ENST00000311189	ENSP00000309845	0.001	2.72	DELETERIOUS
rs104894227	533553	K117R	ENSG00000174775	ENST00000397594	ENSP00000380722	0.001	2.84	DELETERIOUS
rs104894227	533553	K117R	ENSG00000174775	ENST00000397596	ENSP00000380723	0.001	2.72	DELETERIOUS
rs104894227	533553	K117R	ENSG00000174775	ENST00000417302	ENSP00000388246	0.001	2.84	DELETERIOUS
rs104894227	533553	K117R	ENSG00000174775	ENST00000451590	ENSP00000407586	0.001	2.72	DELETERIOUS
rs104894231	533467	A146T	ENSG00000174775	ENST00000311189	ENSP00000309845	0	2.72	DELETERIOUS
rs104894231	533467	A146T	ENSG00000174775	ENST00000397594	ENSP00000380722	0	2.86	DELETERIOUS
rs104894231	533467	A146T	ENSG00000174775	ENST00000397596	ENSP00000380723	0	2.72	DELETERIOUS
rs104894231	533467	A146T	ENSG00000174775	ENST00000417302	ENSP00000388246	0	2.86	DELETERIOUS
rs104894231	533467	A146T	ENSG00000174775	ENST00000451590	ENSP00000407586	0	2.72	DELETERIOUS
rs121917756	533869	E63K	ENSG00000174775	ENST00000311189	ENSP00000309845	0.002	2.73	DELETERIOUS
rs121917756	533869	E63K	ENSG00000174775	ENST00000397596	ENSP00000380723	0.002	2.73	DELETERIOUS
rs121917756	533869	E63K	ENSG00000174775	ENST00000451590	ENSP00000407586	0.002	2.73	DELETERIOUS
rs121917756	533869	E63K	ENSG00000174775	ENST00000397594	ENSP00000380722	0.022	2.87	DELETERIOUS
rs121917756	533869	E63K	ENSG00000174775	ENST00000417302	ENSP00000388246	0.022	2.87	DELETERIOUS
rs121917757	534259	Q22K	ENSG00000174775	ENST00000311189	ENSP00000309845	0.001	2.71	DELETERIOUS
rs121917757	534259	Q22K	ENSG00000174775	ENST00000397594	ENSP00000380722	0.001	2.83	DELETERIOUS
rs121917757	534259	Q22K	ENSG00000174775	ENST00000397596	ENSP00000380723	0.001	2.71	DELETERIOUS
rs121917757	534259	Q22K	ENSG00000174775	ENST00000417302	ENSP00000388246	0.001	2.83	DELETERIOUS
rs121917757	534259	Q22K	ENSG00000174775	ENST00000451590	ENSP00000407586	0.001	2.71	DELETERIOUS
rs121917758	533883	T58I	ENSG00000174775	ENST00000311189	ENSP00000309845	0	2.72	DELETERIOUS
rs121917758	533883	T58I	ENSG00000174775	ENST00000397594	ENSP00000380722	0	2.85	DELETERIOUS
rs121917758	533883	T58I	ENSG00000174775	ENST00000397596	ENSP00000380723	0	2.72	DELETERIOUS
rs121917758	533883	T58I	ENSG00000174775	ENST00000417302	ENSP00000388246	0	2.85	DELETERIOUS
rs121917758	533883	T58I	ENSG00000174775	ENST00000451590	ENSP00000407586	0	2.72	DELETERIOUS

Evolutionary analysis of coding SNPs

SNP Id’s	Amino Acid Change	probability of deleterious effect	Prediction Score
rs28933406	Q61K	probably benign	0.42
rs28933406	Q61K	probably damaging	0.77
rs28933406	Q61K	probably benign	0.5
rs28933406	Q61K	possibly damaging	0.5
rs28933406	Q61K	possibly damaging	0.5
rs104894226	G13V	probably damaging	0.57
rs104894226	G13V	probably damaging	0.67
rs104894226	G13V	probably damaging	0.98
rs104894226	G13V	probably damaging	0.57
rs104894226	G13V	probably damaging	0.65
rs104894226	G13D	probably damaging	0.86
rs104894226	G13D	possibly damaging	0.5
rs104894226	G13D	probably damaging	0.86
rs104894226	G13D	probably damaging	0.86
rs104894226	G13D	probably damaging	0.86
rs104894227	K117R	probably damaging	0.89
rs104894227	K117R	probably damaging	0.89
rs104894227	K117R	probably damaging	0.86
rs104894227	K117R	probably damaging	0.86
rs104894227	K117R	probably damaging	0.89
rs104894231	A146T	probably damaging	0.89
rs104894231	A146T	probability of deleterious effect	0.56
rs104894231	A146T	probably benign	0.62
rs104894231	A146T	probably damaging	0.57
rs104894231	A146T	probably benign	0.27
rs121917756	E63K	possibly damaging	0.5
rs121917756	E63K	possibly damaging	0.5
rs121917756	E63K	probably damaging	0.57
rs121917756	E63K	probably damaging	0.89
rs121917756	E63K	probably damaging	0.86
rs121917757	Q22K	probably damaging	0.86
rs121917757	Q22K	probably damaging	0.86
rs121917757	Q22K	probably damaging	0.86
rs121917757	Q22K	possibly damaging	0.5
rs121917757	Q22K	probably damaging	0.86
rs121917758	T58I	probably damaging	0.86
rs121917758	T58I	probably damaging	0.86
rs121917758	T58I	probably damaging	0.89
rs121917758	T58I	probably damaging	0.89
rs121917758	T58I	probably damaging	0.86

Provean

SNP Id’s	Amino Acid Change	probability	Prediction	Score

rs28933406	Q61K	Deleterious	Damaging	-3.64
rs28933406	Q61K	Deleterious	Damaging	-3.64
rs28933406	Q61K	Deleterious	Damaging	-3.64
rs28933406	Q61K	Deleterious	Damaging	-3.63
rs28933406	Q61K	Deleterious	Damaging	-3.63
rs104894226	G13V	Deleterious	Damaging	-7.61
rs104894226	G13V	Deleterious	Damaging	-7.61
rs104894226	G13V	Deleterious	Damaging	-7.65
rs104894226	G13V	Deleterious	Damaging	-7.65
rs104894226	G13V	Deleterious	Damaging	-7.65
rs104894226	G13D	Deleterious	Damaging	-5.45
rs104894226	G13D	Deleterious	Damaging	-5.45
rs104894226	G13D	Deleterious	Damaging	-5.48
rs104894226	G13D	Deleterious	Damaging	-5.48
rs104894226	G13D	Deleterious	Damaging	-5.48
rs104894227	K117R	Deleterious	Damaging	-2.77
rs104894227	K117R	Deleterious	Damaging	-2.67
rs104894227	K117R	Deleterious	Damaging	-2.77
rs104894227	K117R	Deleterious	Damaging	-2.67
rs104894227	K117R	Deleterious	Damaging	-2.77
rs104894231	A146T	Deleterious	Damaging	-3.67
rs104894231	A146T	Deleterious	Damaging	-3.55
rs104894231	A146T	Deleterious	Damaging	-3.67
rs104894231	A146T	Deleterious	Damaging	-3.55
rs104894231	A146T	Deleterious	Damaging	-3.67
rs121917756	E63K	Deleterious	Damaging	-3.7
rs121917756	E63K	Deleterious	Damaging	-3.7
rs121917756	E63K	Deleterious	Damaging	-3.7
rs121917756	E63K	Deleterious	Damaging	-3.65
rs121917756	E63K	Deleterious	Damaging	-3.65
rs121917757	Q22K	Deleterious	Damaging	-3.36
rs121917757	Q22K	Deleterious	Damaging	-3.34
rs121917757	Q22K	Deleterious	Damaging	-3.36
rs121917757	Q22K	Deleterious	Damaging	-3.34
rs121917757	Q22K	Deleterious	Damaging	-3.36
rs121917758	T58I	Deleterious	Damaging	-5.82
rs121917758	T58I	Deleterious	Damaging	-5.8
rs121917758	T58I	Deleterious	Damaging	-5.82
rs121917758	T58I	Deleterious	Damaging	-5.8
rs121917758	T58I	Deleterious	Damaging	-5.82

SNAP 2

Wildetype Amino Acid	Position	Variant Amino Acid	Predicted Effect	Score	Expected Accurancy
Q	61	K	Effect	96	80%
Q	61	K	Effect	86	70%
Q	61	K	Effect	56	75%
Q	61	K	Effect	36	69%
Q	61	K	Effect	34	65%
G	13	V	Effect	26	36%
G	13	V	Effect	25	45%
G	13	V	Effect	39	82%
G	13	V	Effect	73	46%
G	13	V	Neutral	96	35%
G	13	D	Neutral	35	75%
G	13	D	Effect	15	26%
G	13	D	Neutral	-29	15%
G	13	D	Neutral	57	69%
G	13	D	Neutral	56	78%
K	117	R	Effect	66	63%
K	117	R	Effect	33	45%
K	117	R	Effect	26	25%
K	117	R	Neutral	85	78%
K	117	R	Neutral	56	96%
A	146	T	Effect	65	35%
A	146	T	Effect	45	95%
A	146	T	Effect	26	45%
A	146	T	Neutral	26	98%
A	146	T	Neutral	-52	89%
E	63	K	Neutral	96	75%
E	63	K	Effect	79	96%
E	63	K	Effect	96	54%
E	63	K	Effect	56	26%
E	63	K	Neutral	25	78%
Q	22	K	Neutral	36	96%
Q	22	K	Neutral	24	54%
Q	22	K	Effect	75	26%
Q	22	K	Effect	98	98%
Q	22	K	Effect	85	98%
T	58	I	Effect	96	78%
T	58	I	Neutral	86	98%
T	58	I	Neutral	56	76%
T	58	I	Neutral	24	98%
T	58	I	Effect	98	78%

Polyphen 2

Rs_Id	Mutation Probability	Score
rs28933406	Probably damaging	0.999
rs28933406	Probably damaging	0.999
rs28933406	Possibly damaging	1.00
rs28933406	Possibly damaging	0.98
rs28933406	Probably damaging	0.999
rs104894226	Possibly damaging	0.98
rs104894226	Possibly damaging	0.98
rs104894226	Possibly damaging	1.00
rs104894226	Possibly damaging	1.00
rs104894226	Possibly damaging	0.98
rs104894226	Probably damaging	0.999
rs104894226	Possibly damaging	0.98
rs104894226	Possibly damaging	1.00
rs104894226	Possibly damaging	1.00
rs104894226	Probably damaging	0.999
rs104894227	Probably damaging	0.999
rs104894227	Possibly damaging	1.00
rs104894227	Probably damaging	0.98
rs104894227	Probably damaging	0.98
rs104894227	Possibly damaging	0.98
rs104894231	Possibly damaging	1.00
rs104894231	Possibly damaging	0.98
rs104894231	Possibly damaging	1.00
rs104894231	Possibly damaging	0.98
rs104894231	Probably damaging	0.98
rs121917756	Probably damaging	0.999
rs121917756	Probably damaging	0.999
rs121917756	Possibly damaging	1.00
rs121917756	Possibly damaging	1.00
rs121917756	Possibly damaging	0.98
rs121917757	Probably damaging	0.999
rs121917757	Possibly damaging	0.98
rs121917757	Possibly damaging	1.00
rs121917757	Probably damaging	0.999
rs121917757	Possibly damaging	0.98
rs121917758	Possibly damaging	1.00
rs121917758	Possibly damaging	1.00
rs121917758	Probably damaging	0.98

Hope Prediction

Rs_Ids	Mutation	Mapping Issues	AA Variant	Function Impact	Score
rs28933406	HRAS _Q61K	Uniprot Residue:A	Q61K	High	10.84
rs28933406	HRAS _Q61K		Q61K	Medium	3.88
rs28933406	HRAS _Q61K		Q61K	Medium	4.46
rs28933406	HRAS _Q61K		Q61K	High	5.94
rs28933406	HRAS _Q61K		Q61K	High	10.8
rs104894226	HRAS _G13V		G13V	High	6.52
rs104894226	HRAS _G13V	Uniprot Residue:I	G13V	Medium	4.66
rs104894226	HRAS _G13V		G13V	Medium	4
rs104894226	HRAS _G13V		G13V	Low	0.82
rs104894226	HRAS _G13V	Uniprot Residue:L	G13V	Medium	5.23
rs104894226	HRAS _G13D		G13D	High	10.8
rs104894226	HRAS _G13D		G13D	Medium	4.88
rs104894226	HRAS _G13D		G13D	Medium	4.56
rs104894226	HRAS _G13D		G13D	High	5.94
rs104894226	HRAS _G13D		G13D	High	10.8
rs104894227	HRAS _K117R	Uniprot Residue:T	K117R	High	6.52
rs104894227	HRAS _K117R		K117R	Medium	4.66
rs104894227	HRAS _K117R		K117R	Low	0.59
rs104894227	HRAS _K117R		K117R	Medium	3.16
rs104894227	HRAS _K117R		K117R	Medium	4.26
rs104894231	HRAS _A146T	Uniprot Residue:C	A146T	High	6.62
rs104894231	HRAS _A146T		A146T	Low	0.98
rs104894231	HRAS _A146T		A146T	Medium	4.56
rs104894231	HRAS _A146T		A146T	Medium	3.67
rs104894231	HRAS _A146T		A146T	Medium	2.86
rs121917756	HRAS _E63K	Uniprot Residue:N	E63K	Low	0.65
rs121917756	HRAS _E63K		E63K	High	6.62
rs121917756	HRAS _E63K		E63K	Medium	2.96
rs121917756	HRAS _E63K		E63K	High	8.02
rs121917756	HRAS _E63K		E63K	Medium	4.60
rs121917757	HRAS _Q22K		Q22K	Medium	3.96
rs121917757	HRAS _Q22K	Uniprot Residue:P	Q22K	Low	0.42

10. Active Site

Rank	C-Score	Cluster Size	PDB Hit	Lig Name	Consensus Building Residues
1	1.00	1264	3oesA	GNP	12,13,14,15,16, 17,18,28,29,30,31, 32,34,35,60,116,117, 119,120,145,146,147
2	0.12	111	4fmcD	MG	17,35,57,58
3	0.09	102	2fg5A	MG	17,35
4	0.04	32	4epwA	0QV	5,6,7,37,39,54, 56,67,71,74,75
5	0.04	20	2msdB	GNP	13,15,16,17,18, 28,29,30,31,32, 33,34,35,116,117, 145,146,147
6	0.04	32	4lucA	20G	7,9,10,12,13,34, 58,60,61,68,71, 72,96,99,100
7	0.04	46	4hlqB	BEF	12,13,16,35,58, 59,60
8	0.02	12	4dlsA	CA	102,103
9	0.01	6	2ce2X	XY2	21,25,32,33,36,40
10	0.01	6	1g16A	CO	22,26,149

11. Primary Sequence Analysis

Number of amino acids

189

Molecular weight

21298.13

Theoretical pI

5.16

Amino acid composition

Ala (A) 11 5.8%

Arg (R) 12 6.3%

Asn (N) 5 2.6%

Asp (D) 15 7.9%

Cys (C) 6 3.2%

Gln (Q) 11 5.8%

Glu (E) 14 7.4%

Gly (G) 13 6.9%

His (H) 3 1.6%

Ile (I) 11 5.8%

Leu (L) 14 7.4%

Lys (K) 11 5.8%

Met (M) 5 2.6%

Phe (F) 5 2.6%

Pro (P) 6 3.2%

Ser (S) 11 5.8%

Thr (T) 11 5.8%

Trp (W) 0 0.0%

Tyr (Y) 9 4.8%

Val (V) 16 8.5%

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

C₉₂₆H₁₄₇₈N₂₅₈O₂₉₅S₁₁

Total number of atoms(12269)

2968

Instability index(II)

43.27

Stability

unstable

Aliphatic index(AI)

81.96

GRAVY

-0.417

12. Secondary structure analysis

Alpha helix (Hh) : 74 is 39.15%

310 helix (Gg) : 0 is 0.00%

Pi helix (Ii) : 0 is 0.00%

Beta bridge (Bb) : 0 is 0.00%

Extended strand (Ee) : 38 is 20.11%

Beta turn (Tt) : 0 is 0.00%

Bend region (Ss) : 0 is 0.00%

Random coil (Cc) : 77 is 40.74%

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	12
Asp-N endopeptidase	15
Asp-N endopeptidase + N-terminal Glu	29
CNBr	5
Chymotrypsin-high specificity (C-term to [FYW], not before P)	14
Chymotrypsin-low specificity (C-term to [FYWML], not before P)	36
Clostripain	12
Formic acid	15
Glutamyl endopeptidase	14
LysC	11
LysN	11
NTCB (2-nitro-5-thiocyanobenzoic acid)	6
Pepsin (pH1.3)	30
Pepsin (pH>2)	42
Proteinase K	91
Staphylococcal peptidase I	13
Thermolysin	53
Trypsin	23

14. Epitope

Rank	Start position	Sequence	Score	Prediction
1	6	LVVVGAGGVGKSALTI	0.89	Epitope
1	144	TSAKTRQGVEDAFYTL	0.89	Epitope
2	95	QYREQIKRVKDSDDVP	0.85	Epitope
2	28	FVDEYDPTIEDSYRKQ	0.85	Epitope
2	12	GGVGKSALTIQLIQNH	0.85	Epitope
2	101	KRVKDSDDVPMVLVGN	0.85	Epitope
3	125	VESRQAQDLARSYGIP	0.83	Epitope
4	67	MRDQYMRTGEGFLCVF	0.82	Epitope
5	168	LRKLNPPDESGPGCMS	0.81	Epitope
5	152	VEDAFYTLVREIRQHK	0.81	Epitope
6	59	AGQEEYSAMRDQYMRT	0.77	Epitope
7	43	QVVIDGETCLLDILDT	0.76	Epitope
8	74	TGEGFLCVFAINNTKS	0.75	Epitope
8	158	TLVREIRQHKLRKLNP	0.75	Epitope
9	37	EDSYRKQVVIDGETCL	0.74	Epitope
10	136	SYGIPYIETSAKTRQG	0.72	Epitope
10	118	CDLAARTVESRQAQDL	0.72	Epitope
11	111	MVLVGNKCDLAARTVE	0.69	Epitope
12	21	IQLIQNHFVDEYDPTI	0.64	Epitope
13	50	TCLLDILDTAGQEEYS	0.62	Epitope
13	174	PDESGPGCMSCKCVLS	0.62	Epitope

15. Protein-Protein Interaction

No of Nodes	11
No of Edges	40
Avg node degree	7.27
avg. local clustering coefficient	0.819
expected number of e, dges	16
p-value	3.86e-07
Protein – Protein Interaction network

16. MRNA

RNA Base Pairing Probability Plot