IGDRPT (Indian Genetic Disease Risk Prediction Tool)

Disease Name: Non-syndromic Hearing Loss (DFNB1A)

1 .Inheritance

Autosomal Recessive

2. Gene Name

GJB2

3. Protein Name

Gap junction beta-2 protein

4. Chromosomal Location

13q11-q12

5. Protein Sequence

>sp|P29033|CXB2_HUMAN Gap junction beta-2 protein OS=Homo sapiens OX=9606 GN=GJB2 PE=1 SV=3

MDWGTLQTILGGVNKHSTSIGKIWLTVLFIFRIMILVVAAKEVWGDEQADFVCNTLQPGC

KNVCYDHYFPISHIRLWALQLIFVSTPALLVAMHVAYRRHEKKRKFIKGEIKSEFKDIEE

IKTQKVRIEGSLWWTYTSSIFFRVIFEAAFMYVFYVMYDGFSMQRLVKCNAWPCPNTVDC

FVSRPTEKTVFTVFMIAVSGICILLNVTELCYLLIRYCSGKSKKPV

6. Gene Sequence

>NM_004004.5 Homo sapiens gap junction protein beta 2 (GJB2), mRNA

GGGGTGCGGTTAAAAGGCGCCACGGCGGGAGACAGGTGTTGCGGCCCCGCAGCGCCCGCGCGCTCCTCTC

CCCGACTCGGAGCCCCTCGGCGGCGCCCGGCCCAGGACCCGCCTAGGAGCGCAGGAGCCCCAGCGCAGAG

ACCCCAACGCCGAGACCCCCGCCCCGGCCCCGCCGCGCTTCCTCCCGACGCAGAGCAAACCGCCCAGAGT

AGAAGATGGATTGGGGCACGCTGCAGACGATCCTGGGGGGTGTGAACAAACACTCCACCAGCATTGGAAA

GATCTGGCTCACCGTCCTCTTCATTTTTCGCATTATGATCCTCGTTGTGGCTGCAAAGGAGGTGTGGGGA

GATGAGCAGGCCGACTTTGTCTGCAACACCCTGCAGCCAGGCTGCAAGAACGTGTGCTACGATCACTACT

TCCCCATCTCCCACATCCGGCTATGGGCCCTGCAGCTGATCTTCGTGTCCACGCCAGCGCTCCTAGTGGC

CATGCACGTGGCCTACCGGAGACATGAGAAGAAGAGGAAGTTCATCAAGGGGGAGATAAAGAGTGAATTT

AAGGACATCGAGGAGATCAAAACCCAGAAGGTCCGCATCGAAGGCTCCCTGTGGTGGACCTACACAAGCA

GCATCTTCTTCCGGGTCATCTTCGAAGCCGCCTTCATGTACGTCTTCTATGTCATGTACGACGGCTTCTC

CATGCAGCGGCTGGTGAAGTGCAACGCCTGGCCTTGTCCCAACACTGTGGACTGCTTTGTGTCCCGGCCC

ACGGAGAAGACTGTCTTCACAGTGTTCATGATTGCAGTGTCTGGAATTTGCATCCTGCTGAATGTCACTG

AATTGTGTTATTTGCTAATTAGATATTGTTCTGGGAAGTCAAAAAAGCCAGTTTAACGCATTGCCCAGTT

GTTAGATTAAGAAATAGACAGCATGAGAGGGATGAGGCAACCCGTGCTCAGCTGTCAAGGCTCAGTCGCT

AGCATTTCCCAACACAAAGATTCTGACCTTAAATGCAACCATTTGAAACCCCTGTAGGCCTCAGGTGAAA

CTCCAGATGCCACAATGGAGCTCTGCTCCCCTAAAGCCTCAAAACAAAGGCCTAATTCTATGCCTGTCTT

AATTTTCTTTCACTTAAGTTAGTTCCACTGAGACCCCAGGCTGTTAGGGGTTATTGGTGTAAGGTACTTT

CATATTTTAAACAGAGGATATCGGCATTTGTTTCTTTCTCTGAGGACAAGAGAAAAAAGCCAGGTTCCAC

AGAGGACACAGAGAAGGTTTGGGTGTCCTCCTGGGGTTCTTTTTGCCAACTTTCCCCACGTTAAAGGTGA

ACATTGGTTCTTTCATTTGCTTTGGAAGTTTTAATCTCTAACAGTGGACAAAGTTACCAGTGCCTTAAAC

TCTGTTACACTTTTTGGAAGTGAAAACTTTGTAGTATGATAGGTTATTTTGATGTAAAGATGTTCTGGAT

ACCATTATATGTTCCCCCTGTTTCAGAGGCTCAGATTGTAATATGTAAATGGTATGTCATTCGCTACTAT

GATTTAATTTGAAATATGGTCTTTTGGTTATGAATACTTTGCAGCACAGCTGAGAGGCTGTCTGTTGTAT

TCATTGTGGTCATAGCACCTAACAACATTGTAGCCTCAATCGAGTGAGACAGACTAGAAGTTCCTAGTGA

TGGCTTATGATAGCAAATGGCCTCATGTCAAATATTTAGATGTAATTTTGTGTAAGAAATACAGACTGGA

TGTACCACCAACTACTACCTGTAATGACAGGCCTGTCCAACACATCTCCCTTTTCCATGACTGTGGTAGC

CAGCATCGGAAAGAACGCTGATTTAAAGAGGTCGCTTGGGAATTTTATTGACACAGTACCATTTAATGGG

GAGGACAAAATGGGGCAGGGGAGGGAGAAGTTTCTGTCGTTAAAAACAGATTTGGAAAGACTGGACTCTA

AAGTCTGTTGATTAAAGATGAGCTTTGTCTACTTCAAAAGTTTGTTTGCTTACCCCTTCAGCCTCCAATT

TTTTAAGTGAAAATATAGCTAATAACATGTGAAAAGAATAGAAGCTAAGGTTTAGATAAATATTGAGCAG

ATCTATAGGAAGATTGAACCTGAATATTGCCATTATGCTTGACATGGTTTCCAAAAAATGGTACTCCACA

TATTTCAGTGAGGGTAAGTATTTTCCTGTTGTCAAGAATAGCATTGTAAAAGCATTTTGTAATAATAAAG

AATAGCTTTAATGATATGCTTGTAACTAAAATAATTTTGTAATGTATCAAATACATTTAAAACATTAAAA

TATAATCTCTATAATAATTTAAAAAAAAAAAAAAAAA

7. Motif

Pfam (1 motif)

Pfam

Position(Independent E-value)

Description

Connexin

2..214(3.4e-93)

PF00029, Connexin

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 (-3610.45) 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 395 positions in the final dataset.

9. SNP

SNP	COORDINATE	AMINO ACID CHANGE	GENE ID	TRANSCRIPT ID	PROTEIN ID	SIFT SCORE	SIFT MEDIAN	SIFT PREDICTION
rs1801002	20763686	G12V	ENSG00000165474	ENST00000382844	ENSP00000372295	0.011	2.64	DELETERIOUS
rs1801002	20763686	G12V	ENSG00000165474	ENST00000382848	ENSP00000372299	0.011	2.64	DELETERIOUS
rs28929485	20763671	S17F	ENSG00000165474	ENST00000382844	ENSP00000372295	0	2.64	DELETERIOUS
rs28929485	20763671	S17F	ENSG00000165474	ENST00000382848	ENSP00000372299	0	2.64	DELETERIOUS
rs28931593	20763497	R75Q	ENSG00000165474	ENST00000382844	ENSP00000372295	0.001	2.63	DELETERIOUS
rs28931593	20763497	R75Q	ENSG00000165474	ENST00000382848	ENSP00000372299	0.001	2.63	DELETERIOUS
rs28931594	20763573	D50Y	ENSG00000165474	ENST00000382844	ENSP00000372295	0.001	2.63	DELETERIOUS
rs28931594	20763573	D50Y	ENSG00000165474	ENST00000382848	ENSP00000372299	0.001	2.63	DELETERIOUS
rs28931594	20763573	D50N	ENSG00000165474	ENST00000382844	ENSP00000372295	0.106	2.63	TOLERATED
rs28931594	20763573	D50N	ENSG00000165474	ENST00000382848	ENSP00000372299	0.106	2.63	TOLERATED
rs28931595	20763186	D179N	ENSG00000165474	ENST00000382844	ENSP00000372295	0.119	2.63	TOLERATED
rs28931595	20763186	D179N	ENSG00000165474	ENST00000382848	ENSP00000372299	0.119	2.63	TOLERATED
rs35887622	20763620	M34R	ENSG00000165474	ENST00000382844	ENSP00000372295	0	2.63	DELETERIOUS
rs35887622	20763620	M34R	ENSG00000165474	ENST00000382848	ENSP00000372299	0	2.63	DELETERIOUS
rs35887622	20763620	M34T	ENSG00000165474	ENST00000382844	ENSP00000372295	0.013	2.63	DELETERIOUS
rs35887622	20763620	M34T	ENSG00000165474	ENST00000382848	ENSP00000372299	0.013	2.63	DELETERIOUS
rs72474224	20763612	V37I	ENSG00000165474	ENST00000382844	ENSP00000372295	0.51	2.63	TOLERATED
rs72474224	20763612	V37I	ENSG00000165474	ENST00000382848	ENSP00000372299	0.51	2.63	TOLERATED
rs72561723	20763587	G45E	ENSG00000165474	ENST00000382844	ENSP00000372295	0.022	2.63	DELETERIOUS
rs72561723	20763587	G45E	ENSG00000165474	ENST00000382848	ENSP00000372299	0.022	2.63	DELETERIOUS
rs76434661	20763305	S139N	ENSG00000165474	ENST00000382844	ENSP00000372295	0.169	2.63	TOLERATED
rs76434661	20763305	S139N	ENSG00000165474	ENST00000382848	ENSP00000372299	0.169	2.63	TOLERATED
rs80338941	20763665	S19T	ENSG00000165474	ENST00000382844	ENSP00000372295	0.062	2.64	TOLERATED
rs80338941	20763665	S19T	ENSG00000165474	ENST00000382848	ENSP00000372299	0.062	2.64	TOLERATED
rs80338944	20763490	W77*	ENSG00000165474	ENST00000382844	ENSP00000372295
rs80338944	20763490	W77*	ENSG00000165474	ENST00000382848	ENSP00000372299
rs80338945	20763452	L90P	ENSG00000165474	ENST00000382844	ENSP00000372295	0.001	2.63	DELETERIOUS
rs80338945	20763452	L90P	ENSG00000165474	ENST00000382848	ENSP00000372299	0.001	2.63	DELETERIOUS
rs80338948	20763294	R143W	ENSG00000165474	ENST00000382844	ENSP00000372295	0	2.63	DELETERIOUS
rs80338948	20763294	R143W	ENSG00000165474	ENST00000382848	ENSP00000372299	0	2.63	DELETERIOUS
rs80338949	20763234	M163V	ENSG00000165474	ENST00000382844	ENSP00000372295	0.168	2.63	TOLERATED
rs80338949	20763234	M163V	ENSG00000165474	ENST00000382848	ENSP00000372299	0.168	2.63	TOLERATED
rs80338950	20763170	R184P	ENSG00000165474	ENST00000382844	ENSP00000372295	0	2.63	DELETERIOUS
rs80338950	20763170	R184P	ENSG00000165474	ENST00000382848	ENSP00000372299	0	2.63	DELETERIOUS
rs80338950	20763170	R184Q	ENSG00000165474	ENST00000382844	ENSP00000372295	0.001	2.63	DELETERIOUS
rs80338950	20763170	R184Q	ENSG00000165474	ENST00000382848	ENSP00000372299	0.001	2.63	DELETERIOUS
rs104894395	20763491	W77*	ENSG00000165474	ENST00000382844	ENSP00000372295
rs104894395	20763491	W77*	ENSG00000165474	ENST00000382848	ENSP00000372299
rs104894396	20763650	W24*	ENSG00000165474	ENST00000382844	ENSP00000372295
rs104894396	20763650	W24*	ENSG00000165474	ENST00000382848	ENSP00000372299
rs104894397	20763492	W77R	ENSG00000165474	ENST00000382844	ENSP00000372295	0	2.63	DELETERIOUS
rs104894397	20763492	W77R	ENSG00000165474	ENST00000382848	ENSP00000372299	0	2.63	DELETERIOUS
rs104894398	20763582	E47*	ENSG00000165474	ENST00000382844	ENSP00000372295
rs104894398	20763582	E47*	ENSG00000165474	ENST00000382848	ENSP00000372299
rs104894401	20763293	R143Q	ENSG00000165474	ENST00000382844	ENSP00000372295	0.003	2.63	DELETERIOUS
rs104894401	20763293	R143Q	ENSG00000165474	ENST00000382848	ENSP00000372299	0.003	2.63	DELETERIOUS
rs104894402	20763498	R75W	ENSG00000165474	ENST00000382844	ENSP00000372295	0	2.63	DELETERIOUS
rs104894402	20763498	R75W	ENSG00000165474	ENST00000382848	ENSP00000372299	0	2.63	DELETERIOUS
rs104894403	20763525	D66H	ENSG00000165474	ENST00000382844	ENSP00000372295	0	2.63	DELETERIOUS
rs104894403	20763525	D66H	ENSG00000165474	ENST00000382848	ENSP00000372299	0	2.63	DELETERIOUS
rs104894404	20763545	G59A	ENSG00000165474	ENST00000382844	ENSP00000372295	0	2.63	DELETERIOUS
rs104894404	20763545	G59A	ENSG00000165474	ENST00000382848	ENSP00000372299	0	2.63	DELETERIOUS
rs104894406	20763116	C202F	ENSG00000165474	ENST00000382844	ENSP00000372295	0.038	2.63	DELETERIOUS
rs104894406	20763116	C202F	ENSG00000165474	ENST00000382848	ENSP00000372299	0.038	2.63	DELETERIOUS
rs104894407	20763589	W44C	ENSG00000165474	ENST00000382844	ENSP00000372295	0	2.63	DELETERIOUS
rs104894407	20763589	W44C	ENSG00000165474	ENST00000382848	ENSP00000372299	0	2.63	DELETERIOUS
rs104894408	20763687	G12C	ENSG00000165474	ENST00000382844	ENSP00000372295	0.005	2.64	DELETERIOUS
rs104894408	20763687	G12C	ENSG00000165474	ENST00000382848	ENSP00000372299	0.005	2.64	DELETERIOUS
rs104894408	20763687	G12R	ENSG00000165474	ENST00000382844	ENSP00000372295	0.038	2.64	DELETERIOUS
rs104894408	20763687	G12R	ENSG00000165474	ENST00000382848	ENSP00000372299	0.038	2.64	DELETERIOUS
rs104894409	20763471	V84L	ENSG00000165474	ENST00000382844	ENSP00000372295	0.001	2.62	DELETERIOUS
rs104894409	20763471	V84L	ENSG00000165474	ENST00000382848	ENSP00000372299	0.001	2.62	DELETERIOUS
rs104894409	20763471	V84M	ENSG00000165474	ENST00000382844	ENSP00000372295	0	2.62	DELETERIOUS
rs104894409	20763471	V84M	ENSG00000165474	ENST00000382848	ENSP00000372299	0	2.62	DELETERIOUS
rs104894410	20763546	G59S	ENSG00000165474	ENST00000382844	ENSP00000372295	0	2.63	DELETERIOUS
rs104894410	20763546	G59S	ENSG00000165474	ENST00000382848	ENSP00000372299	0	2.63	DELETERIOUS
rs104894412	20763559	N54K	ENSG00000165474	ENST00000382844	ENSP00000372295	0.001	2.63	DELETERIOUS
rs104894412	20763559	N54K	ENSG00000165474	ENST00000382848	ENSP00000372299	0.001	2.63	DELETERIOUS
rs104894413	20763590	W44S	ENSG00000165474	ENST00000382844	ENSP00000372295	0	2.63	DELETERIOUS
rs104894413	20763590	W44S	ENSG00000165474	ENST00000382848	ENSP00000372299	0	2.63	DELETERIOUS
rs111033190	20763626	R32H	ENSG00000165474	ENST00000382844	ENSP00000372295	0	2.63	DELETERIOUS
rs111033190	20763626	R32H	ENSG00000165474	ENST00000382848	ENSP00000372299	0	2.63	DELETERIOUS
rs111033217	20763677	K15T	ENSG00000165474	ENST00000382844	ENSP00000372295	0.135	2.64	TOLERATED
rs111033217	20763677	K15T	ENSG00000165474	ENST00000382848	ENSP00000372299	0.135	2.64	TOLERATED
rs111033293	20763720	M1V	ENSG00000165474	ENST00000382844	ENSP00000372295	0.02	3.12	DELETERIOUS
rs111033293	20763720	M1V	ENSG00000165474	ENST00000382848	ENSP00000372299	0.02	3.12	DELETERIOUS
rs111033294	20763104	N206S	ENSG00000165474	ENST00000382844	ENSP00000372295	0.182	2.63	TOLERATED
rs111033294	20763104	N206S	ENSG00000165474	ENST00000382848	ENSP00000372299	0.182	2.63	TOLERATED
rs111033295	20763356	K122I	ENSG00000165474	ENST00000382844	ENSP00000372295	0.043	2.66	DELETERIOUS
rs111033295	20763356	K122I	ENSG00000165474	ENST00000382848	ENSP00000372299	0.043	2.66	DELETERIOUS
rs111033297	20763552	Q57*	ENSG00000165474	ENST00000382844	ENSP00000372295
rs111033297	20763552	Q57*	ENSG00000165474	ENST00000382848	ENSP00000372299
rs111033299	20763438	V95M	ENSG00000165474	ENST00000382844	ENSP00000372295	0.024	2.63	DELETERIOUS
rs111033299	20763438	V95M	ENSG00000165474	ENST00000382848	ENSP00000372299	0.024	2.63	DELETERIOUS
rs111033401	20763712	W3*	ENSG00000165474	ENST00000382844	ENSP00000372295
rs111033401	20763712	W3*	ENSG00000165474	ENST00000382848	ENSP00000372299
rs111033451	20763702	Q7*	ENSG00000165474	ENST00000382844	ENSP00000372295
rs111033451	20763702	Q7*	ENSG00000165474	ENST00000382848	ENSP00000372299
rs121912968	20763503	H73R	ENSG00000165474	ENST00000382844	ENSP00000372295	0.011	2.63	DELETERIOUS
rs121912968	20763503	H73R	ENSG00000165474	ENST00000382848	ENSP00000372299	0.011	2.63	DELETERIOUS
rs143343083	20763423	H100Y	ENSG00000165474	ENST00000382844	ENSP00000372295	0.05	2.62	TOLERATED
rs143343083	20763423	H100Y	ENSG00000165474	ENST00000382848	ENSP00000372299	0.05	2.62	TOLERATED
rs150529554	20763366	E119K	ENSG00000165474	ENST00000382844	ENSP00000372295	0.363	2.66	TOLERATED
rs150529554	20763366	E119K	ENSG00000165474	ENST00000382848	ENSP00000372299	0.363	2.66	TOLERATED
rs201895089	20763744		ENSG00000165474	ENST00000382844	ENSP00000372295
rs371024165	20763627	R32C	ENSG00000165474	ENST00000382844	ENSP00000372295	0.015	2.63	DELETERIOUS
rs371024165	20763627	R32C	ENSG00000165474	ENST00000382848	ENSP00000372299	0.015	2.63	DELETERIOUS
rs371086981	20763719	M1T	ENSG00000165474	ENST00000382844	ENSP00000372295	0.001	3.12	DELETERIOUS
rs371086981	20763719	M1T	ENSG00000165474	ENST00000382848	ENSP00000372299	0.001	3.12	DELETERIOUS
rs375759781	20763247	Y158Y	ENSG00000165474	ENST00000382844	ENSP00000372295	1	2.63	TOLERATED
rs375759781	20763247	Y158Y	ENSG00000165474	ENST00000382848	ENSP00000372299	1	2.63	TOLERATED

Evolutionary analysis of coding SNPs

SNP	Substitution	Probability of deleterious effect	Prediction Score
rs1801002	G12V	probably damaging	0.57
rs1801002	G12V	probably damaging	0.57
rs28929485	S17F	probably damaging	0.74
rs28929485	S17F	probably damaging	0.74
rs28931593	R75Q	probably damaging	0.74
rs28931593	R75Q	probably damaging	0.74
rs28931594	D50Y	probably damaging	0.57
rs28931594	D50Y	probably damaging	0.57
rs28931594	D50N	probably damaging	0.57
rs28931594	D50N	probably damaging	0.57
rs28931595	D179N	probably damaging	0.74
rs28931595	D179N	probably damaging	0.74
rs35887622	M34R	probably damaging	0.57
rs35887622	M34R	probably damaging	0.57
rs35887622	M34T	probably damaging	0.57
rs35887622	M34T	probably damaging	0.57
rs72474224	V37I	probably damaging	0.57
rs72474224	V37I	probably damaging	0.57
rs72561723	G45E	probably damaging	0.74
rs72561723	G45E	probably damaging	0.74
rs76434661	S139N	probably damaging	0.57
rs76434661	S139N	probably damaging	0.57
rs80338941	S19T	probably damaging	0.57
rs80338941	S19T	probably damaging	0.57
rs80338944	L90P	probably damaging	0.57
rs80338944	L90P	probably damaging	0.57
rs80338945	R143W	probably damaging	0.74
rs80338945	R143W	probably damaging	0.74
rs80338948	M163V	probably damaging	0.57
rs80338948	M163V	probably damaging	0.57
rs80338949	R184P	probably damaging	0.74
rs80338949	R184P	probably damaging	0.74
rs80338950	R184Q	probably damaging	0.74
rs80338950	R184Q	probably damaging	0.74
rs80338950	W77R	probably damaging	0.74
rs80338950	W77R	probably damaging	0.74
rs104894395	R143Q	probably damaging	0.74
rs104894395	R143Q	probably damaging	0.74
rs104894396	R75W	probably damaging	0.74
rs104894396	R75W	probably damaging	0.74
rs104894397	D66H	probably damaging	0.74
rs104894397	D66H	probably damaging	0.74
rs104894398	G59A	probably damaging	0.74
rs104894398	G59A	probably damaging	0.74
rs104894401	C202F	probably damaging	0.74
rs104894401	C202F	probably damaging	0.74
rs104894402	W44C	probably damaging	0.74
rs104894402	W44C	probably damaging	0.74
rs104894403	G12C	probably damaging	0.57
rs104894403	G12C	probably damaging	0.57
rs104894404	G12R	probably damaging	0.57
rs104894404	G12R	probably damaging	0.57
rs104894406	V84L	probably damaging	0.74
rs104894406	V84L	probably damaging	0.74
rs104894407	V84M	probably damaging	0.74
rs104894407	V84M	probably damaging	0.74
rs104894408	G59S	probably damaging	0.74
rs104894408	G59S	probably damaging	0.74
rs104894408	N54K	probably damaging	0.74
rs104894408	N54K	probably damaging	0.74
rs104894409	W44S	probably damaging	0.74
rs104894409	W44S	probably damaging	0.74
rs104894409	R32H	probably damaging	0.74
rs104894409	R32H	probably damaging	0.74
rs104894410	K15T	possibly damaging	0.5
rs104894410	K15T	possibly damaging	0.5
rs104894412	M1V	probably damaging	0.57
rs104894412	M1V	probably damaging	0.57
rs104894413	N206S	probably damaging	0.74
rs104894413	N206S	probably damaging	0.74
rs111033190	K122I	probably damaging	0.57
rs111033190	K122I	probably damaging	0.57
rs111033217	V95M	probably benign	0.27
rs111033217	V95M	probably benign	0.27
rs111033293	H73R	probably damaging	0.74
rs111033293	H73R	probably damaging	0.74
rs111033294	H100Y	possibly damaging	0.5
rs111033294	H100Y	possibly damaging	0.5
rs111033295	E119K	probably damaging	0.57
rs111033295	E119K	probably damaging	0.57
rs111033297	R32C	probably damaging	0.74
rs111033297	R32C	probably damaging	0.74
rs111033299	M1T	probably damaging	0.57
rs111033299	M1T	probably damaging	0.57
rs111033401	Y158Y	probably damaging	0.74
rs111033401	Y158Y	probably damaging	0.74

Provean

SNP Id’s	Amino Acid Change	Probability	Prediction	Score
rs1801002	G12V	Deleterious	Damaging	-8.27
rs1801002	G12V	Deleterious	Damaging	-8.27
rs28929485	S17F	Deleterious	Damaging	-5.73
rs28929485	S17F	Deleterious	Damaging	-5.73
rs28931593	R75Q	Deleterious	Damaging	-4
rs28931593	R75Q	Deleterious	Damaging	-4
rs28931594	D50Y	Deleterious	Damaging	-6.52
rs28931594	D50Y	Deleterious	Damaging	-6.52
rs28931594	D50N	Deleterious	Damaging	-3.27
rs28931594	D50N	Deleterious	Damaging	-3.27
rs28931595	D179N	Deleterious	Damaging	-4.66
rs28931595	D179N	Deleterious	Tolerated	-4.66
rs35887622	M34R	Deleterious	Tolerated	-4.47
rs35887622	M34R	Deleterious	Damaging	-4.47
rs35887622	M34T	Deleterious	Damaging	-3.8
rs35887622	M34T	Deleterious	Damaging	-3.8
rs72474224	V37I	Neutral	Damaging	-0.82
rs72474224	V37I	Neutral	Tolerated	-0.82
rs72561723	G45E	Deleterious	Tolerated	-5.23
rs72561723	G45E	Deleterious	Damaging	-5.23
rs76434661	S139N	Deleterious	Damaging	-2.62
rs76434661	S139N	Deleterious	Tolerated	-2.62
rs80338941	S19T	Neutral	Tolerated	-1.59
rs80338941	S19T	Neutral	Tolerated	-1.59
rs80338945	L90P	Deleterious	Tolerated	-6.62
rs80338945	L90P	Deleterious	Damaging	-6.62
rs80338948	R143W	Deleterious	Damaging	-6.25
rs80338948	R143W	Deleterious	Damaging	-6.25
rs80338949	M163V	Neutral	Damaging	-2.16
rs80338949	M163V		Tolerated
rs80338950	R184P	Deleterious		-6.08
rs80338950	R184P	Deleterious	Damaging	-6.08
rs80338950	R184Q	Deleterious	Damaging	-3.35
rs80338950	R184Q	Deleterious	Damaging	-3.35
rs104894397	W77R	Deleterious	Damaging	-14
rs104894397	W77R	Deleterious	Damaging	-14
rs104894401	R143Q	Neutral	Damaging	-2.29
rs104894401	R143Q	Neutral	Damaging	-2.29
rs104894402	R75W		Damaging
rs104894402	R75W	Deleterious		-7.99
rs104894403	D66H	Deleterious	Damaging	-6.99
rs104894403	D66H	Deleterious	Damaging	-6.99
rs104894404	G59A	Deleterious	Damaging	-5.94
rs104894404	G59A	Deleterious	Damaging	-5.94
rs104894406	C202F	Deleterious	Damaging	-10.2
rs104894406	C202F	Deleterious	Damaging	-10.2
rs104894407	W44C	Deleterious	Damaging	-12.8
rs104894407	W44C	Deleterious	Damaging	-12.8
rs104894408	G12C	Deleterious	Damaging	-8.32
rs104894408	G12C	Deleterious	Damaging	-8.32
rs104894408	G12R	Deleterious	Damaging	-7.06
rs104894408	G12R	Deleterious	Damaging	-7.06
rs104894409	V84L	Deleterious	Damaging	-3
rs104894409	V84L	Deleterious	Damaging	-3
rs104894409	V84M	Deleterious	Damaging	-3
rs104894409	V84M	Deleterious	Damaging	-3
rs104894410	G59S	Deleterious	Damaging	-5.94
rs104894410	G59S	Deleterious	Damaging	-5.94
rs104894412	N54K	Deleterious	Damaging	-5.93
rs104894412	N54K	Deleterious	Damaging	-5.93
rs104894413	W44S	Deleterious	Damaging	-13.8
rs104894413	W44S	Deleterious	Damaging	-13.8
rs111033190	R32H	Deleterious	Damaging	-4.88
rs111033190	R32H	Deleterious	Damaging	-4.88
rs111033217	K15T	Deleterious	Damaging	-4.56
rs111033217	K15T	Deleterious	Damaging	-4.56
rs111033293	M1V	Deleterious	Damaging	-3.68
rs111033293	M1V	Deleterious	Damaging	-3.68
rs111033294	N206S	Deleterious	Damaging	-3.8
rs111033294	N206S	Deleterious	Tolerated	-3.8
rs111033295	K122I	Deleterious	Tolerated	-3.37
rs111033295	K122I	Deleterious	Tolerated	-3.37
rs111033299	V95M	Deleterious	Tolerated	-2.9
rs111033299	V95M	Deleterious	Damaging	-2.9
rs121912968	H73R	Deleterious	Damaging	-7.17
rs121912968	H73R	Deleterious	Damaging	-7.17
rs143343083	H100Y	Deleterious	Damaging	-3.42
rs143343083	H100Y	Deleterious	Tolerated	-3.42
rs150529554	E119K	Neutral	Tolerated	-1.25
rs150529554	E119K	Neutral	Tolerated	-1.25
rs371024165	R32C	Deleterious	Tolerated	-7.78
rs371024165	R32C		Damaging
rs371086981	M1T	Deleterious		-5.49
rs371086981	M1T	Deleterious	Damaging	-5.49
rs375759781	Y158Y	Neutral	Damaging	0
rs375759781	Y158Y	Neutral	Tolerated	0

SNAP2

Wildetype Amino Acid	Position	Variant Amino Acid	Predicted Effect	Score	Expected Accurancy
G	12	V	Effect	78	98%
G	12	V	Effect	56	78%
S	17	F	Effect	56	98%
S	17	F	Effect	85	76%
R	75	Q	Effect	96	98%
R	75	Q	Effect	75	78%
D	50	Y	Effect	26	98%
D	50	Y	Effect	24	76%
D	50	N	Effect	98	98%
D	179	N	Effect	75	78%
D	179	N	Effect	65	98%
D	179	N	Effect	42	76%
M	34	R	Effect	35	98%
M	34	R	Effect	-29	78%
M	34	T	Effect	56	98%
M	34	T	Effect	36	76%
V	37	I	Effect	75	98%
V	37	I	Effect	63	76%
G	45	E	Effect	36	98%
G	45	E	Effect	25	78%
S	139	N	Effect	36	98%
S	139	N	Effect	45	76%
S	19	T	Effect	26	98%
S	19	T	Effect	26	98%
L	90	P	Effect	-52	76%
L	90	P	Effect	96	98%
R	143	W	Effect	79	78%
R	143	W	Neutral	96	98%
M	163	V	Neutral	56	76%
M	163	V	Neutral	25	98%
R	184	P	Effect	36	78%
R	184	P	Effect	24	98%
R	184	Q	Effect	75	76%
R	184	Q	Neutral	98	98%
W	77	R	Effect	65	76%
W	77	R	Effect	45	98%
R	143	Q	Effect	46	78%
R	143	Q	Effect	25	98%
R	75	W	Effect	26	76%
R	75	W	Effect	79	98%
D	66	H	Effect	36	78%
G	59	A	Effect	25	98%
G	59	A	Effect	46	76%
G	59	A	Effect	56	98%
C	202	F	Effect	56	78%
C	202	F	Effect	28	98%
W	44	C	Effect	36	76%
W	44	C	Effect	36	98%
G	12	C	Effect	14	76%
G	12	C	Effect	25	98%
G	12	R	Effect	76	78%
G	12	R	Effect	85	98%
V	84	L	Effect	26	76%
V	84	L	Effect	46	98%
V	84	M	Effect	76	78%
V	84	M	Effect	72	98%
G	59	S	Effect	53	76%
G	59	s	Effect	46	98%
N	54	K	Effect	96	78%
N	54	K	Effect	43	98%
W	44	S	Effect	79	76%
W	44	S	Effect	85	98%
R	32	H	Effect	72	76%
R	32	H	Effect	53	98%
K	15	T	Effect	67	78%
K	15	T	Effect	67	89%
M	1	V	Effect	76	75%
M	1	V	Effect	26	65%
N	206	S	Effect	46	75%
N	206	S	Neutral	36	90%

Polyphen2

Rs_Id	Mutation Probability	Score
rs1801002	Possibly damaging	1.00
rs1801002	Probably damaging	0.98
rs28929485	Possibly damaging	1.00
rs28929485	Probably damaging	0.999
rs28931593	Probably damaging	0.999
rs28931593	Probably damaging	0.98
rs28931594	Possibly damaging	1.00
rs28931594	Probably damaging	0.999
rs28931594	Possibly damaging	1.00
rs28931594	Probably damaging	1.00
rs28931595	Probably damaging	0.98
rs28931595	Possibly damaging	0.999
rs35887622	Probably damaging	0.999
rs35887622	Possibly damaging	0.999
rs35887622	Probably damaging	1.00
rs35887622	Possibly damaging	0.98
rs72474224	Possibly damaging	0.999
rs72474224	Probably damaging	1.00
rs72561723	Probably damaging	0.98
rs72561723	Possibly damaging	1.00
rs76434661	Possibly damaging	0.999
rs76434661	Possibly damaging	0.999
rs80338941	Probably damaging	0.98
rs80338941	Possibly damaging	1.00
rs80338945	Probably damaging	0.999
rs80338945	Possibly damaging	1.00
rs80338948	Probably damaging	1.00
rs80338948	Probably damaging	0.98
rs80338949	Possibly damaging	0.999
rs80338949	Probably damaging	0.999
rs80338950	Possibly damaging	0.999
rs80338950	Possibly damaging	1.00
rs80338950	Probably damaging	0.999
rs80338950	Probably damaging	0.999
rs104894397	Possibly damaging	1.00
rs104894397	Probably damaging	0.999
rs104894401	Probably damaging	0.999
rs104894401	Probably damaging	0.999
rs104894402	Possibly damaging	0.98
rs104894402	Possibly damaging	1.00
rs104894403	Probably damaging	0.999
rs104894403	Probably damaging	0.98
rs104894404	Possibly damaging	0.98
rs104894404	Possibly damaging	1.00
rs104894406	Probably damaging	0.98
rs104894406	Possibly damaging	1.00
rs104894407	Probably damaging	0.999
rs104894407	Probably damaging	0.999
rs104894408	Possibly damaging	1.00
rs104894408	Probably damaging	0.999

Hope Prediction

Rs_Ids	Mutation	Mapping Issues	AA Variant	Function Impact	Score
rs1801002	GJB2_G12V		G12V	High	6.52
rs28929485	GJB2_S17F	Uniprot Residue:G	S17F	Medium	4.66
rs28931593	GJB2_R75Q		R75Q	Medium	4
rs28931594	GJB2_D50Y		D50Y	Low	0.82
rs28931595	GJB2_D179N		D179N	Medium	5.23
rs35887622	GJB2_M34R	Uniprot Residue:N	M34R	Medium	5.23
rs72474224	GJB2_V37I		V37I	Medium	2.62
rs72561723	GJB2_G45E		G45E	Medium	2.62
rs72561723	GJB2_G45E		G45E	Low	1.59
rs76434661	GJB2_S139N		S139N	Medium	2.16
rs76434661	GJB2_S139N		S139N	Medium	2.16
rs80338941	GJB2_S19T	Uniprot Residue:c	S19T	High	6.62
rs80338941	GJB2_S19T		S19T	High	6.62
rs80338945	GJB2_L90P		L90P	Medium	2.16
rs80338948	GJB2_R143W		R143W	High	6.25
rs80338949	GJB2_M163V		M163V	Medium	2.16
rs80338950	GJB2_R184P		R184P	Medium	2.29
rs104894397	GJB2_W77R		W77R	High	7.99
rs104894401	GJB2_R143Q	Uniprot Residue:C	R143Q	Medium	2.29
rs104894402	GJB2_R75W		R75W	High	6.99
rs104894403	GJB2_D66H	Uniprot Residue:N	D66H	High	5.94
rs104894404	GJB2_G59A		G59A	High	5.94
rs104894406	GJB2_C202F		C202F	High	10.2
rs104894407	GJB2_W44C	Uniprot Residue:R	W44C	High	6.99
rs104894408	GJB2_G12C		G12C	High	5.94
rs104894408	GJB2_G12R		G12R	High	5.94
rs104894409	GJB2_V84L		V84L	High	10.2
rs104894409	GJB2_V84M		V84M	High	6.99
rs104894410	GJB2_G59S		G59S	High	5.94
rs104894412	GJB2_N54K	Uniprot Residue:T	N54K	High	5.94
rs104894413	GJB2_W44S		W44S	High	10.8
rs111033190	GJB2_R32H		R32H	Medium	4.88
rs111033217	GJB2_K15T		K15T	Medium	4.56
rs111033293	GJB2_M1V	Uniprot Residue:P	M1V	Medium	3.68
rs111033294	GJB2_N206S		N206S	Medium	3.8
rs111033295	GJB2_K122I		K122I	Medium	3.37
rs111033299	GJB2_V95M		V95M	Medium	2.9
rs121912968	GJB2_H73R		H73R	High	7.17
rs143343083	GJB2_H100Y	Uniprot Residue:N	H100Y	Medium	3.42
rs150529554	GJB2_E119K		E119K	Low	1.25
rs371024165	GJB2_R32C		R32C	High	7.78
rs371086981	GJB2_M1T		M1T	High	5.49
rs3757597l81	GJB2_Y158Y		Y158Y	Low	0

10. Active Site

Nil

11. Primary Sequence Analysis

Number of amino acids

226

Molecular weight

26215.07

Theoretical pI

9.11

Amino acid composition

Ala (A) 11 4.9%

Arg (R) 10 4.4%

Asn (N) 6 2.7%

Asp (D) 7 3.1%

Cys (C) 9 4.0%

Gln (Q) 6 2.7%

Glu (E) 11 4.9%

Gly (G) 11 4.9%

His (H) 5 2.2%

Ile (I) 20 8.8%

Leu (L) 18 8.0%

Lys (K) 17 7.5%

Met (M) 7 3.1%

Phe (F) 16 7.1%

Pro (P) 7 3.1%

Ser (S) 13 5.8%

Thr (T) 14 6.2%

Trp (W) 7 3.1%

Tyr (Y) 9 4.0%

Val (V) 22 9.7%

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

C₁₂₁₆H₁₈₇₆N₃₀₂O₃₁₁S₁₆

Total number of atoms

3721

Instability index(II)

42.80

Stability

unstable

Aliphatic index(AI)

98.67

GRAVY

0.288

12. Secondary structure analysis

Alpha helix (Hh) : 108 is 47.79%

310 helix (Gg) : 0 is 0.00%

Pi helix (Ii) : 0 is 0.00%

Beta bridge (Bb) : 0 is 0.00%

Extended strand (Ee) : 34 is 15.04%

Beta turn (Tt) : 0 is 0.00%

Bend region (Ss) : 0 is 0.00%

Random coil (Cc) : 84 is 37.17%

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	10
Asp-N endopeptidase	7
Asp-N endopeptidase + N-terminal Glu	18
BNPS-Skatole	7
CNBr	7
Chymotrypsin-high specificity (C-term to [FYW], not before P)	30
Chymotrypsin-low specificity (C-term to [FYWML], not before P)	58
Clostripain	10
Formic acid	7
Glutamylendopeptidase	11
Iodosobenzoic acid	7
LysC	17
LysN	17
NTCB (2-nitro-5-thiocyanobenzoic acid)	9
Pepsin (pH1.3)	51
Pepsin (pH>2)	71
Proline-endopeptidase	2
Proteinase K	128
Staphylococcal peptidase I	10
Thermolysin	84
Trypsin	24

14. Epitope

Rank	Start Position	Sequence	Score	Prediction
1	40	AKEVWGDEQADFVCNT	0.94	Epitope
2	166	LVKCNAWPCPNTVDCF	0.89	Epitope
3	155	YVMYDGFSMQRLVKCN	0.87	Epitope
4	125	KVRIEGSLWWTYTSSI	0.81	Epitope
5	208	TELCYLLIRYCSGKSK	0.80	Epitope
5	20	IGKIWLTVLFIFRIMI	0.80	Epitope
5	11	GGVNKHSTSIGKIWLT	0.80	Epitope
6	172	WPCPNTVDCFVSRPTE	0.79	Epitope
7	97	YRRHEKKRKFIKGEIK	0.78	Epitope
7	3	WGTLQTILGGVNKHST	0.78	Epitope

15. Protein-Protein Interaction

No of Nodes	11
No of Edges	25
Avg node degree	4.55
avg. local clustering coefficient	0.885
expected number of e, dges	10
p-value	5.92e-05
Protein – Protein Interaction network

16. MRNA

RNA Base Pairing Probability Plot