IGDRPT (Indian Genetic Disease Risk Prediction Tool)

Disease Name: Cystic Fibrosis

1 .Inheritance

Autosomal Recessive

2. Gene Name

CFTR

3. Protein Name

Cystic fibrosis transmembrane conductance regulator

4. Chromosomal Location

7q31.2

5. Protein Sequence

>sp|P13569|CFTR_HUMAN Cystic fibrosis transmembrane conductance regulator OS=Homo sapiens OX=9606 GN=CFTR PE=1 SV=3

MQRSPLEKASVVSKLFFSWTRPILRKGYRQRLELSDIYQIPSVDSADNLSEKLEREWDRE

LASKKNPKLINALRRCFFWRFMFYGIFLYLGEVTKAVQPLLLGRIIASYDPDNKEERSIA

IYLGIGLCLLFIVRTLLLHPAIFGLHHIGMQMRIAMFSLIYKKTLKLSSRVLDKISIGQL

VSLLSNNLNKFDEGLALAHFVWIAPLQVALLMGLIWELLQASAFCGLGFLIVLALFQAGL

GRMMMKYRDQRAGKISERLVITSEMIENIQSVKAYCWEEAMEKMIENLRQTELKLTRKAA

YVRYFNSSAFFFSGFFVVFLSVLPYALIKGIILRKIFTTISFCIVLRMAVTRQFPWAVQT

WYDSLGAINKIQDFLQKQEYKTLEYNLTTTEVVMENVTAFWEEGFGELFEKAKQNNNNRK

TSNGDDSLFFSNFSLLGTPVLKDINFKIERGQLLAVAGSTGAGKTSLLMVIMGELEPSEG

KIKHSGRISFCSQFSWIMPGTIKENIIFGVSYDEYRYRSVIKACQLEEDISKFAEKDNIV

LGEGGITLSGGQRARISLARAVYKDADLYLLDSPFGYLDVLTEKEIFESCVCKLMANKTR

ILVTSKMEHLKKADKILILHEGSSYFYGTFSELQNLQPDFSSKLMGCDSFDQFSAERRNS

ILTETLHRFSLEGDAPVSWTETKKQSFKQTGEFGEKRKNSILNPINSIRKFSIVQKTPLQ

MNGIEEDSDEPLERRLSLVPDSEQGEAILPRISVISTGPTLQARRRQSVLNLMTHSVNQG

QNIHRKTTASTRKVSLAPQANLTELDIYSRRLSQETGLEISEEINEEDLKECFFDDMESI

PAVTTWNTYLRYITVHKSLIFVLIWCLVIFLAEVAASLVVLWLLGNTPLQDKGNSTHSRN

NSYAVIITSTSSYYVFYIYVGVADTLLAMGFFRGLPLVHTLITVSKILHHKMLHSVLQAP

MSTLNTLKAGGILNRFSKDIAILDDLLPLTIFDFIQLLLIVIGAIAVVAVLQPYIFVATV

PVIVAFIMLRAYFLQTSQQLKQLESEGRSPIFTHLVTSLKGLWTLRAFGRQPYFETLFHK

ALNLHTANWFLYLSTLRWFQMRIEMIFVIFFIAVTFISILTTGEGEGRVGIILTLAMNIM

STLQWAVNSSIDVDSLMRSVSRVFKFIDMPTEGKPTKSTKPYKNGQLSKVMIIENSHVKK

DDIWPSGGQMTVKDLTAKYTEGGNAILENISFSISPGQRVGLLGRTGSGKSTLLSAFLRL

LNTEGEIQIDGVSWDSITLQQWRKAFGVIPQKVFIFSGTFRKNLDPYEQWSDQEIWKVAD

EVGLRSVIEQFPGKLDFVLVDGGCVLSHGHKQLMCLARSVLSKAKILLLDEPSAHLDPVT

YQIIRRTLKQAFADCTVILCEHRIEAMLECQQFLVIEENKVRQYDSIQKLLNERSLFRQA

ISPSDRVKLFPHRNSSKCKSKPQIAALKEETEEEVQDTRL

6. Gene Sequence

>NM_000492.3 Homo sapiens CF transmembrane conductance regulator (CFTR), mRNA

AATTGGAAGCAAATGACATCACAGCAGGTCAGAGAAAAAGGGTTGAGCGGCAGGCACCCAGAGTAGTAGG

TCTTTGGCATTAGGAGCTTGAGCCCAGACGGCCCTAGCAGGGACCCCAGCGCCCGAGAGACCATGCAGAG

GTCGCCTCTGGAAAAGGCCAGCGTTGTCTCCAAACTTTTTTTCAGCTGGACCAGACCAATTTTGAGGAAA

GGATACAGACAGCGCCTGGAATTGTCAGACATATACCAAATCCCTTCTGTTGATTCTGCTGACAATCTAT

CTGAAAAATTGGAAAGAGAATGGGATAGAGAGCTGGCTTCAAAGAAAAATCCTAAACTCATTAATGCCCT

TCGGCGATGTTTTTTCTGGAGATTTATGTTCTATGGAATCTTTTTATATTTAGGGGAAGTCACCAAAGCA

GTACAGCCTCTCTTACTGGGAAGAATCATAGCTTCCTATGACCCGGATAACAAGGAGGAACGCTCTATCG

CGATTTATCTAGGCATAGGCTTATGCCTTCTCTTTATTGTGAGGACACTGCTCCTACACCCAGCCATTTT

TGGCCTTCATCACATTGGAATGCAGATGAGAATAGCTATGTTTAGTTTGATTTATAAGAAGACTTTAAAG

CTGTCAAGCCGTGTTCTAGATAAAATAAGTATTGGACAACTTGTTAGTCTCCTTTCCAACAACCTGAACA

AATTTGATGAAGGACTTGCATTGGCACATTTCGTGTGGATCGCTCCTTTGCAAGTGGCACTCCTCATGGG

GCTAATCTGGGAGTTGTTACAGGCGTCTGCCTTCTGTGGACTTGGTTTCCTGATAGTCCTTGCCCTTTTT

CAGGCTGGGCTAGGGAGAATGATGATGAAGTACAGAGATCAGAGAGCTGGGAAGATCAGTGAAAGACTTG

TGATTACCTCAGAAATGATTGAAAATATCCAATCTGTTAAGGCATACTGCTGGGAAGAAGCAATGGAAAA

AATGATTGAAAACTTAAGACAAACAGAACTGAAACTGACTCGGAAGGCAGCCTATGTGAGATACTTCAAT

AGCTCAGCCTTCTTCTTCTCAGGGTTCTTTGTGGTGTTTTTATCTGTGCTTCCCTATGCACTAATCAAAG

GAATCATCCTCCGGAAAATATTCACCACCATCTCATTCTGCATTGTTCTGCGCATGGCGGTCACTCGGCA

ATTTCCCTGGGCTGTACAAACATGGTATGACTCTCTTGGAGCAATAAACAAAATACAGGATTTCTTACAA

AAGCAAGAATATAAGACATTGGAATATAACTTAACGACTACAGAAGTAGTGATGGAGAATGTAACAGCCT

TCTGGGAGGAGGGATTTGGGGAATTATTTGAGAAAGCAAAACAAAACAATAACAATAGAAAAACTTCTAA

TGGTGATGACAGCCTCTTCTTCAGTAATTTCTCACTTCTTGGTACTCCTGTCCTGAAAGATATTAATTTC

AAGATAGAAAGAGGACAGTTGTTGGCGGTTGCTGGATCCACTGGAGCAGGCAAGACTTCACTTCTAATGG

TGATTATGGGAGAACTGGAGCCTTCAGAGGGTAAAATTAAGCACAGTGGAAGAATTTCATTCTGTTCTCA

GTTTTCCTGGATTATGCCTGGCACCATTAAAGAAAATATCATCTTTGGTGTTTCCTATGATGAATATAGA

TACAGAAGCGTCATCAAAGCATGCCAACTAGAAGAGGACATCTCCAAGTTTGCAGAGAAAGACAATATAG

TTCTTGGAGAAGGTGGAATCACACTGAGTGGAGGTCAACGAGCAAGAATTTCTTTAGCAAGAGCAGTATA

CAAAGATGCTGATTTGTATTTATTAGACTCTCCTTTTGGATACCTAGATGTTTTAACAGAAAAAGAAATA

TTTGAAAGCTGTGTCTGTAAACTGATGGCTAACAAAACTAGGATTTTGGTCACTTCTAAAATGGAACATT

TAAAGAAAGCTGACAAAATATTAATTTTGCATGAAGGTAGCAGCTATTTTTATGGGACATTTTCAGAACT

CCAAAATCTACAGCCAGACTTTAGCTCAAAACTCATGGGATGTGATTCTTTCGACCAATTTAGTGCAGAA

AGAAGAAATTCAATCCTAACTGAGACCTTACACCGTTTCTCATTAGAAGGAGATGCTCCTGTCTCCTGGA

CAGAAACAAAAAAACAATCTTTTAAACAGACTGGAGAGTTTGGGGAAAAAAGGAAGAATTCTATTCTCAA

TCCAATCAACTCTATACGAAAATTTTCCATTGTGCAAAAGACTCCCTTACAAATGAATGGCATCGAAGAG

GATTCTGATGAGCCTTTAGAGAGAAGGCTGTCCTTAGTACCAGATTCTGAGCAGGGAGAGGCGATACTGC

CTCGCATCAGCGTGATCAGCACTGGCCCCACGCTTCAGGCACGAAGGAGGCAGTCTGTCCTGAACCTGAT

GACACACTCAGTTAACCAAGGTCAGAACATTCACCGAAAGACAACAGCATCCACACGAAAAGTGTCACTG

GCCCCTCAGGCAAACTTGACTGAACTGGATATATATTCAAGAAGGTTATCTCAAGAAACTGGCTTGGAAA

TAAGTGAAGAAATTAACGAAGAAGACTTAAAGGAGTGCTTTTTTGATGATATGGAGAGCATACCAGCAGT

GACTACATGGAACACATACCTTCGATATATTACTGTCCACAAGAGCTTAATTTTTGTGCTAATTTGGTGC

TTAGTAATTTTTCTGGCAGAGGTGGCTGCTTCTTTGGTTGTGCTGTGGCTCCTTGGAAACACTCCTCTTC

AAGACAAAGGGAATAGTACTCATAGTAGAAATAACAGCTATGCAGTGATTATCACCAGCACCAGTTCGTA

TTATGTGTTTTACATTTACGTGGGAGTAGCCGACACTTTGCTTGCTATGGGATTCTTCAGAGGTCTACCA

CTGGTGCATACTCTAATCACAGTGTCGAAAATTTTACACCACAAAATGTTACATTCTGTTCTTCAAGCAC

CTATGTCAACCCTCAACACGTTGAAAGCAGGTGGGATTCTTAATAGATTCTCCAAAGATATAGCAATTTT

GGATGACCTTCTGCCTCTTACCATATTTGACTTCATCCAGTTGTTATTAATTGTGATTGGAGCTATAGCA

GTTGTCGCAGTTTTACAACCCTACATCTTTGTTGCAACAGTGCCAGTGATAGTGGCTTTTATTATGTTGA

GAGCATATTTCCTCCAAACCTCACAGCAACTCAAACAACTGGAATCTGAAGGCAGGAGTCCAATTTTCAC

TCATCTTGTTACAAGCTTAAAAGGACTATGGACACTTCGTGCCTTCGGACGGCAGCCTTACTTTGAAACT

CTGTTCCACAAAGCTCTGAATTTACATACTGCCAACTGGTTCTTGTACCTGTCAACACTGCGCTGGTTCC

AAATGAGAATAGAAATGATTTTTGTCATCTTCTTCATTGCTGTTACCTTCATTTCCATTTTAACAACAGG

AGAAGGAGAAGGAAGAGTTGGTATTATCCTGACTTTAGCCATGAATATCATGAGTACATTGCAGTGGGCT

GTAAACTCCAGCATAGATGTGGATAGCTTGATGCGATCTGTGAGCCGAGTCTTTAAGTTCATTGACATGC

CAACAGAAGGTAAACCTACCAAGTCAACCAAACCATACAAGAATGGCCAACTCTCGAAAGTTATGATTAT

TGAGAATTCACACGTGAAGAAAGATGACATCTGGCCCTCAGGGGGCCAAATGACTGTCAAAGATCTCACA

GCAAAATACACAGAAGGTGGAAATGCCATATTAGAGAACATTTCCTTCTCAATAAGTCCTGGCCAGAGGG

TGGGCCTCTTGGGAAGAACTGGATCAGGGAAGAGTACTTTGTTATCAGCTTTTTTGAGACTACTGAACAC

TGAAGGAGAAATCCAGATCGATGGTGTGTCTTGGGATTCAATAACTTTGCAACAGTGGAGGAAAGCCTTT

GGAGTGATACCACAGAAAGTATTTATTTTTTCTGGAACATTTAGAAAAAACTTGGATCCCTATGAACAGT

GGAGTGATCAAGAAATATGGAAAGTTGCAGATGAGGTTGGGCTCAGATCTGTGATAGAACAGTTTCCTGG

GAAGCTTGACTTTGTCCTTGTGGATGGGGGCTGTGTCCTAAGCCATGGCCACAAGCAGTTGATGTGCTTG

GCTAGATCTGTTCTCAGTAAGGCGAAGATCTTGCTGCTTGATGAACCCAGTGCTCATTTGGATCCAGTAA

CATACCAAATAATTAGAAGAACTCTAAAACAAGCATTTGCTGATTGCACAGTAATTCTCTGTGAACACAG

GATAGAAGCAATGCTGGAATGCCAACAATTTTTGGTCATAGAAGAGAACAAAGTGCGGCAGTACGATTCC

ATCCAGAAACTGCTGAACGAGAGGAGCCTCTTCCGGCAAGCCATCAGCCCCTCCGACAGGGTGAAGCTCT

TTCCCCACCGGAACTCAAGCAAGTGCAAGTCTAAGCCCCAGATTGCTGCTCTGAAAGAGGAGACAGAAGA

AGAGGTGCAAGATACAAGGCTTTAGAGAGCAGCATAAATGTTGACATGGGACATTTGCTCATGGAATTGG

AGCTCGTGGGACAGTCACCTCATGGAATTGGAGCTCGTGGAACAGTTACCTCTGCCTCAGAAAACAAGGA

TGAATTAAGTTTTTTTTTAAAAAAGAAACATTTGGTAAGGGGAATTGAGGACACTGATATGGGTCTTGAT

AAATGGCTTCCTGGCAATAGTCAAATTGTGTGAAAGGTACTTCAAATCCTTGAAGATTTACCACTTGTGT

TTTGCAAGCCAGATTTTCCTGAAAACCCTTGCCATGTGCTAGTAATTGGAAAGGCAGCTCTAAATGTCAA

TCAGCCTAGTTGATCAGCTTATTGTCTAGTGAAACTCGTTAATTTGTAGTGTTGGAGAAGAACTGAAATC

ATACTTCTTAGGGTTATGATTAAGTAATGATAACTGGAAACTTCAGCGGTTTATATAAGCTTGTATTCCT

TTTTCTCTCCTCTCCCCATGATGTTTAGAAACACAACTATATTGTTTGCTAAGCATTCCAACTATCTCAT

TTCCAAGCAAGTATTAGAATACCACAGGAACCACAAGACTGCACATCAAAATATGCCCCATTCAACATCT

AGTGAGCAGTCAGGAAAGAGAACTTCCAGATCCTGGAAATCAGGGTTAGTATTGTCCAGGTCTACCAAAA

ATCTCAATATTTCAGATAATCACAATACATCCCTTACCTGGGAAAGGGCTGTTATAATCTTTCACAGGGG

ACAGGATGGTTCCCTTGATGAAGAAGTTGATATGCCTTTTCCCAACTCCAGAAAGTGACAAGCTCACAGA

CCTTTGAACTAGAGTTTAGCTGGAAAAGTATGTTAGTGCAAATTGTCACAGGACAGCCCTTCTTTCCACA

GAAGCTCCAGGTAGAGGGTGTGTAAGTAGATAGGCCATGGGCACTGTGGGTAGACACACATGAAGTCCAA

GCATTTAGATGTATAGGTTGATGGTGGTATGTTTTCAGGCTAGATGTATGTACTTCATGCTGTCTACACT

AAGAGAGAATGAGAGACACACTGAAGAAGCACCAATCATGAATTAGTTTTATATGCTTCTGTTTTATAAT

TTTGTGAAGCAAAATTTTTTCTCTAGGAAATATTTATTTTAATAATGTTTCAAACATATATAACAATGCT

GTATTTTAAAAGAATGATTATGAATTACATTTGTATAAAATAATTTTTATATTTGAAATATTGACTTTTT

ATGGCACTAGTATTTCTATGAAATATTATGTTAAAACTGGGACAGGGGAGAACCTAGGGTGATATTAACC

AGGGGCCATGAATCACCTTTTGGTCTGGAGGGAAGCCTTGGGGCTGATGCAGTTGTTGCCCACAGCTGTA

TGATTCCCAGCCAGCACAGCCTCTTAGATGCAGTTCTGAAGAAGATGGTACCACCAGTCTGACTGTTTCC

ATCAAGGGTACACTGCCTTCTCAACTCCAAACTGACTCTTAAGAAGACTGCATTATATTTATTACTGTAA

GAAAATATCACTTGTCAATAAAATCCATACATTTGTGTGAAA

7. Motif

Pfam (18 motifs)

Pfam	Position(Independent E-value)	Description
ABC_membrane	82..350(2.2e-45) 863..1147(2.5e-51)	PF00664, ABC transporter transmembrane region
CFTR_R	639..849(5.7e-96)	PF14396, Cystic fibrosis TM conductance regulator (CFTR), regulator domain
ABC_tran	441..575(4.3e-24) 1227..1373(5.9e-30)	PF00005, ABC transporter
SMC_N	1345..1418(0.017)	PF02463, RecF/RecN/SMC N terminal domain
AAA_21	1241..1274(0.3) 1346..1386(0.03)	PF13304, AAA domain, putative AbiEii toxin, Type IV TA system
AAA_29	1234..1265(0.0012)	PF13555, P-loop containing region of AAA domain
DUF87	1238..1262(0.13)	PF01935, Helicase HerA, central domain
AAA_16	1240..1286(0.15)	PF13191, AAA ATPase domain
T2SSE	1243..1264(0.12)	PF00437, Type II/IV secretion system protein
RsgA_GTPase	1243..1264(0.12)	PF03193, RsgA GTPase
DO-GTPase2	1239..1284(0.19)	PF19993, Double-GTPase 2
MeaB	1217..1266(0.0066)	PF03308, Methylmalonyl Co-A mutase-associated GTPase MeaB
AAA_30	1240..1293(0.68)	PF13604, AAA domain
MMR_HSR1	1239..1259(0.62)	PF01926, 50S ribosome-binding GTPase
Zeta_toxin	450..479(0.52)	PF06414, Zeta toxin
AAA_23	1242..1260(0.99)	PF13476, AAA domain
NTPase_1	1240..1289(0.39)	PF03266, NTPase
Intein_splicing	369..516(0.14)	PF14890, Intein splicing 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 (-21132.35) 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 2075 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 damaging	0.87
rs28933406	Q61K	probably damaging	0.87
rs28933406	Q61K	probably damaging	0.87
rs28933406	Q61K	probably damaging	0.87
rs28933406	Q61K	probably damaging	0.87
rs104894226	G13V	probably damaging	0.57
rs104894226	G13V	probably damaging	0.57
rs104894226	G13V	probably damaging	0.57
rs104894226	G13V	probably damaging	0.57
rs104894226	G13V	possibly damaging	0.57
rs104894226	G13D	possibly damaging	0.57
rs104894226	G13D	probably damaging	0.57
rs104894226	G13D	probably damaging	0.57
rs104894226	G13D	possibly damaging	0.57
rs104894226	G13D	possibly damaging	0.57
rs104894227	K117R	possibly damaging	0.53
rs104894227	K117R	probably damaging	0.57
rs104894227	K117R	probably damaging	0.57
rs104894227	K117R	probably damaging	0.57
rs104894227	K117R	probably damaging	0.74
rs104894231	A146T	probably damaging	0.74
rs104894231	A146T	probably damaging	0.74
rs104894231	A146T	probably damaging	0.57
rs104894231	A146T	probably damaging	0.57
rs104894231	A146T	possibly damaging	0.5
rs121917756	E63K	possibly damaging	0.5
rs121917756	E63K	possibly damaging	0.5
rs121917756	E63K	possibly damaging	0.5
rs121917756	E63K	possibly damaging	0.5
rs121917756	E63K	probably damaging	0.74
rs121917757	Q22K	probably damaging	0.74
rs121917757	Q22K	probably damaging	0.74
rs121917757	Q22K	possibly damaging	0.5
rs121917757	Q22K	possibly damaging	0.5
rs121917757	Q22K	probably benign	0.19
rs121917758	T58I	probably benign	0.19
rs121917758	T58I	probably damaging	0.85
rs121917758	T58I	probably damaging	0.85
rs121917758	T58I	probably damaging	0.74
rs121917758	T58I	probably damaging	0.74

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

SNP 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	0.98
rs28933406	Possibly damaging	1.00
rs28933406	Probably damaging	0.98
rs104894226	Possibly damaging	1.00
rs104894226	Possibly damaging	0.98
rs104894226	Possibly damaging	1.00
rs104894226	Probably damaging	0.999
rs104894226	Probably damaging	0.98
rs104894226	Possibly damaging	0.98
rs104894226	Possibly damaging	1.00
rs104894226	Probably damaging	0.98
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	Probably damaging	0.98
rs121917756	Probably damaging	0.98
rs121917757	Possibly damaging	0.98
rs121917757	Possibly damaging	1.00
rs121917757	Possibly damaging	0.98
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 issue	AA variant	Function. Impact	Score
rs28933406	CFTR_Q61K		Q61K	High	5.64
rs104894226	CFTR_G13V	Uniprot residue:R	G13V
rs104894226	CFTR_G13D		G13D	High	5.45
rs104894227	CFTR_K117R		K117R	Medium	3.77
rs104894231	CFTR_A146T	Uniprot residue:P	A146T
rs121917756	CFTR_E63K		E63K	Medium	2.7
rs121917757	CFTR_Q22K	Uniprot residue:G	Q22K
rs121917758	CFTR_T58I		T58I	Low	1.82

10. Active Site

Nil

11. Primary Sequence Analysis

Number of amino acids

1480

Molecular weight

168141.57

Theoretical pI

8.91

Amino acid composition

Ala (A) 83 5.6%

Arg (R) 78 5.3%

Asn (N) 54 3.6%

Asp (D) 58 3.9%

Cys (C) 18 1.2%

Gln (Q) 67 4.5%

Glu (E) 93 6.3%

Gly (G) 84 5.7%

His (H) 25 1.7%

Ile (I) 119 8.0%

Leu (L) 183 12.4%

Lys (K) 92 6.2%

Met (M) 37 2.5%

Phe (F) 85 5.7%

Pro (P) 45 3.0%

Ser (S) 123 8.3%

Thr (T) 83 5.6%

Trp (W) 23 1.6%

Tyr (Y) 40 2.7%

Val (V) 90 6.1%

Pyl (O) 0 0.0%

Sec (U) 0 0.0%

Total number of negatively charged residues (Asp + Glu)

151

Total number of positively charged residues (Arg + Lys)

170

Formula

C₇₆₄₀H₁₂₁₀₆N₂₀₀₀O₂₁₅₀S₅₅

Total number of atoms

23951

Instability index(II)

43.80

Stability

unstable

Aliphatic index(AI)

102.82

GRAVY

0.024

12. Secondary structure analysis

Alpha helix (Hh) : 767 is 51.82%

310 helix (Gg) : 0 is 0.00%

Pi helix (Ii) : 0 is 0.00%

Beta bridge (Bb) : 0 is 0.00%

Extended strand (Ee) : 147 is 9.93%

Beta turn (Tt) : 0 is 0.00%

Bend region (Ss) : 0 is 0.00%

Random coil (Cc) : 566 is 38.24%

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	78
Asp-N endopeptidase	58
Asp-N endopeptidase + N-terminal Glu	151
BNPS-Skatole	23
CNBr	37
Chymotrypsin-high specificity (C-term to [FYW], not before P)	144
Chymotrypsin-low specificity (C-term to [FYWML], not before P)	382
Clostripain	78
Factor Xa	1
Formic acid	58
Glutamyl endopeptidase	93
Iodosobenzoic acid	23
Hydroxylamine	3
LysC	92
LysN	92
NTCB (2-nitro-5-thiocyanobenzoic acid)	18
Pepsin (pH1.3)	377
Pepsin (pH>2)	457
Proline-endopeptidase	5
Proteinase K	799
Staphylococcal peptidase I	82
Thermolysin	536
Thrombin	1
Trypsin	165

14. Epitope

Rank	Start position	Sequence	Score	Prediction
1	1164	FKFIDMPTEGKPTKST	0.95	Epitope
2	725	EEDSDEPLERRLSLVP	0.94	Epitope
2	102	LGRIIASYDPDNKEER	0.94	Epitope
3	499	PGTIKENIIFGVSYDE	0.93	Epitope
4	621	EGSSYFYGTFSELQNL	0.92	Epitope
5	241	GRMMMKYRDQRAGKIS	0.91	Epitope
5	212	MGLIWELLQASAFCGL	0.91	Epitope
6	887	TPLQDKGNSTHSRNNS	0.89	Epitope
6	717	TPLQMNGIEEDSDEPL	0.89	Epitope
6	583	EKEIFESCVCKLMANK	0.89	Epitope
6	1291	QKVFIFSGTFRKNLDP	0.89	Epitope
7	789	ASTRKVSLAPQANLTE	0.88	Epitope
8	881	LWLLGNTPLQDKGNST	0.87	Epitope
8	731	PLERRLSLVPDSEQGE	0.87	Epitope
8	493	QFSWIMPGTIKENIIF	0.87	Epitope
9	685	QSFKQTGEFGEKRKNS	0.86	Epitope
9	670	SLEGDAPVSWTETKKQ	0.86	Epitope
9	649	SFDQFSAERRNSILTE	0.86	Epitope
9	524	CQLEEDISKFAEKDNI	0.86	Epitope
9	52	KLEREWDRELASKKNP	0.86	Epitope
9	509	GVSYDEYRYRSVIKAC	0.86	Epitope
9	1107	FVIFFIAVTFISILTT	0.86	Epitope
10	676	PVSWTETKKQSFKQTG	0.85	Epitope
10	543	EGGITLSGGQRARISL	0.85	Epitope
10	1440	AISPSDRVKLFPHRNS	0.85	Epitope
10	1116	FISILTTGEGEGRVGI	0.85	Epitope
11	600	RILVTSKMEHLKKADK	0.84	Epitope
11	355	PWAVQTWYDSLGAINK	0.84	Epitope
11	16	FFSWTRPILRKGYRQR	0.84	Epitope
11	1264	EGEIQIDGVSWDSITL	0.84	Epitope
12	468	LMVIMGELEPSEGKIK	0.83	Epitope
12	1381	YQIIRRTLKQAFADCT	0.83	Epitope
12	1363	KAKILLLDEPSAHLDP	0.83	Epitope
13	998	LLIVIGAIAVVAVLQP	0.82	Epitope
13	920	VGVADTLLAMGFFRGL	0.82	Epitope
13	752	ISVISTGPTLQARRRQ	0.82	Epitope
13	664	ETLHRFSLEGDAPVSW	0.82	Epitope
13	275	YCWEEAMEKMIENLRQ	0.82	Epitope
13	1306	PYEQWSDQEIWKVADE	0.82	Epitope
13	1214	DLTAKYTEGGNAILEN	0.82	Epitope
14	908	TSTSSYYVFYIYVGVA	0.81	Epitope

15. Protein-Protein Interaction

No of Nodes	11
No of Edges	49
Avg node degree	8.91
avg. local clustering coefficient	0.952
expected number of edges	13
p-value	1.05e-14
Protein – Protein Interaction network

16. MRNA

RNA Base Pairing Probability Plot