IGDRPT (Indian Genetic Disease Risk Prediction Tool)

Disease Name: Arrhythmogenic right ventricular dysplasia

1 .Inheritance

Autosomal Dominant

2. Gene Name

RYR2

3. Protein Name

Ryanodine receptor 2

4. Chromosomal Location

1q43

5. Protein Sequence

>sp|Q92736|RYR2_HUMAN Ryanodine receptor 2 OS=Homo sapiens OX=9606 GN=RYR2 PE=1 SV=3

MADGGEGEDEIQFLRTDDEVVLQCTATIHKEQQKLCLAAEGFGNRLCFLESTSNSKNVPP

DLSICTFVLEQSLSVRALQEMLANTVEKSEGQVDVEKWKFMMKTAQGGGHRTLLYGHAIL

LRHSYSGMYLCCLSTSRSSTDKLAFDVGLQEDTTGEACWWTIHPASKQRSEGEKVRVGDD

LILVSVSSERYLHLSYGNGSLHVDAAFQQTLWSVAPISSGSEAAQGYLIGGDVLRLLHGH

MDECLTVPSGEHGEEQRRTVHYEGGAVSVHARSLWRLETLRVAWSGSHIRWGQPFRLRHV

TTGKYLSLMEDKNLLLMDKEKADVKSTAFTFRSSKEKLDVGVRKEVDGMGTSEIKYGDSV

CYIQHVDTGLWLTYQSVDVKSVRMGSIQRKAIMHHEGHMDDGISLSRSQHEESRTARVIR

STVFLFNRFIRGLDALSKKAKASTVDLPIESVSLSLQDLIGYFHPPDEHLEHEDKQNRLR

ALKNRQNLFQEEGMINLVLECIDRLHVYSSAAHFADVAGREAGESWKSILNSLYELLAAL

IRGNRKNCAQFSGSLDWLISRLERLEASSGILEVLHCVLVESPEALNIIKEGHIKSIISL

LDKHGRNHKVLDVLCSLCVCHGVAVRSNQHLICDNLLPGRDLLLQTRLVNHVSSMRPNIF

LGVSEGSAQYKKWYYELMVDHTEPFVTAEATHLRVGWASTEGYSPYPGGGEEWGGNGVGD

DLFSYGFDGLHLWSGCIARTVSSPNQHLLRTDDVISCCLDLSAPSISFRINGQPVQGMFE

NFNIDGLFFPVVSFSAGIKVRFLLGGRHGEFKFLPPPGYAPCYEAVLPKEKLKVEHSREY

KQERTYTRDLLGPTVSLTQAAFTPIPVDTSQIVLPPHLERIREKLAENIHELWVMNKIEL

GWQYGPVRDDNKRQHPCLVEFSKLPEQERNYNLQMSLETLKTLLALGCHVGISDEHAEDK

VKKMKLPKNYQLTSGYKPAPMDLSFIKLTPSQEAMVDKLAENAHNVWARDRIRQGWTYGI

QQDVKNRRNPRLVPYTLLDDRTKKSNKDSLREAVRTLLGYGYNLEAPDQDHAARAEVCSG

TGERFRIFRAEKTYAVKAGRWYFEFETVTAGDMRVGWSRPGCQPDQELGSDERAFAFDGF

KAQRWHQGNEHYGRSWQAGDVVGCMVDMNEHTMMFTLNGEILLDDSGSELAFKDFDVGDG

FIPVCSLGVAQVGRMNFGKDVSTLKYFTICGLQEGYEPFAVNTNRDITMWLSKRLPQFLQ

VPSNHEHIEVTRIDGTIDSSPCLKVTQKSFGSQNSNTDIMFYRLSMPIECAEVFSKTVAG

GLPGAGLFGPKNDLEDYDADSDFEVLMKTAHGHLVPDRVDKDKEATKPEFNNHKDYAQEK

PSRLKQRFLLRRTKPDYSTSHSARLTEDVLADDRDDYDFLMQTSTYYYSVRIFPGQEPAN

VWVGWITSDFHQYDTGFDLDRVRTVTVTLGDEKGKVHESIKRSNCYMVCAGESMSPGQGR

NNNGLEIGCVVDAASGLLTFIANGKELSTYYQVEPSTKLFPAVFAQATSPNVFQFELGRI

KNVMPLSAGLFKSEHKNPVPQCPPRLHVQFLSHVLWSRMPNQFLKVDVSRISERQGWLVQ

CLDPLQFMSLHIPEENRSVDILELTEQEELLKFHYHTLRLYSAVCALGNHRVAHALCSHV

DEPQLLYAIENKYMPGLLRAGYYDLLIDIHLSSYATARLMMNNEYIVPMTEETKSITLFP

DENKKHGLPGIGLSTSLRPRMQFSSPSFVSISNECYQYSPEFPLDILKSKTIQMLTEAVK

EGSLHARDPVGGTTEFLFVPLIKLFYTLLIMGIFHNEDLKHILQLIEPSVFKEAATPEEE

SDTLEKELSVDDAKLQGAGEEEAKGGKRPKEGLLQMKLPEPVKLQMCLLLQYLCDCQVRH

RIEAIVAFSDDFVAKLQDNQRFRYNEVMQALNMSAALTARKTKEFRSPPQEQINMLLNFK

DDKSECPCPEEIRDQLLDFHEDLMTHCGIELDEDGSLDGNSDLTIRGRLLSLVEKVTYLK

KKQAEKPVESDSKKSSTLQQLISETMVRWAQESVIEDPELVRAMFVLLHRQYDGIGGLVR

ALPKTYTINGVSVEDTINLLASLGQIRSLLSVRMGKEEEKLMIRGLGDIMNNKVFYQHPN

LMRALGMHETVMEVMVNVLGGGESKEITFPKMVANCCRFLCYFCRISRQNQKAMFDHLSY

LLENSSVGLASPAMRGSTPLDVAAASVMDNNELALALREPDLEKVVRYLAGCGLQSCQML

VSKGYPDIGWNPVEGERYLDFLRFAVFCNGESVEENANVVVRLLIRRPECFGPALRGEGG

NGLLAAMEEAIKIAEDPSRDGPSPNSGSSKTLDTEEEEDDTIHMGNAIMTFYSALIDLLG

RCAPEMHLIHAGKGEAIRIRSILRSLIPLGDLVGVISIAFQMPTIAKDGNVVEPDMSAGF

CPDHKAAMVLFLDRVYGIEVQDFLLHLLEVGFLPDLRAAASLDTAALSATDMALALNRYL

CTAVLPLLTRCAPLFAGTEHHASLIDSLLHTVYRLSKGCSLTKAQRDSIEVCLLSICGQL

RPSMMQHLLRRLVFDVPLLNEHAKMPLKLLTNHYERCWKYYCLPGGWGNFGAASEEELHL

SRKLFWGIFDALSQKKYEQELFKLALPCLSAVAGALPPDYMESNYVSMMEKQSSMDSEGN

FNPQPVDTSNITIPEKLEYFINKYAEHSHDKWSMDKLANGWIYGEIYSDSSKVQPLMKPY

KLLSEKEKEIYRWPIKESLKTMLAWGWRIERTREGDSMALYNRTRRISQTSQVSVDAAHG

YSPRAIDMSNVTLSRDLHAMAEMMAENYHNIWAKKKKMELESKGGGNHPLLVPYDTLTAK

EKAKDREKAQDILKFLQINGYAVSRGFKDLELDTPSIEKRFAYSFLQQLIRYVDEAHQYI

LEFDGGSRGKGEHFPYEQEIKFFAKVVLPLIDQYFKNHRLYFLSAASRPLCSGGHASNKE

KEMVTSLFCKLGVLVRHRISLFGNDATSIVNCLHILGQTLDARTVMKTGLESVKSALRAF

LDNAAEDLEKTMENLKQGQFTHTRNQPKGVTQIINYTTVALLPMLSSLFEHIGQHQFGED

LILEDVQVSCYRILTSLYALGTSKSIYVERQRSALGECLAAFAGAFPVAFLETHLDKHNI

YSIYNTKSSRERAALSLPTNVEDVCPNIPSLEKLMEEIVELAESGIRYTQMPHVMEVILP

MLCSYMSRWWEHGPENNPERAEMCCTALNSEHMNTLLGNILKIIYNNLGIDEGAWMKRLA

VFSQPIINKVKPQLLKTHFLPLMEKLKKKAATVVSEEDHLKAEARGDMSEAELLILDEFT

TLARDLYAFYPLLIRFVDYNRAKWLKEPNPEAEELFRMVAEVFIYWSKSHNFKREEQNFV

VQNEINNMSFLITDTKSKMSKAAVSDQERKKMKRKGDRYSMQTSLIVAALKRLLPIGLNI

CAPGDQELIALAKNRFSLKDTEDEVRDIIRSNIHLQGKLEDPAIRWQMALYKDLPNRTDD

TSDPEKTVERVLDIANVLFHLEQKSKRVGRRHYCLVEHPQRSKKAVWHKLLSKQRKRAVV

ACFRMAPLYNLPRHRAVNLFLQGYEKSWIETEEHYFEDKLIEDLAKPGAEPPEEDEGTKR

VDPLHQLILLFSRTALTEKCKLEEDFLYMAYADIMAKSCHDEEDD

6. Gene Sequence

>NM_001035.3 Homo sapiens ryanodine receptor 2 (RYR2), mRNA

ACTTGCTCGGAGGAGCCGGGGCCGAGCGGACCGCCGGCTGCAGGCAGCGAGCGCGGCTGGGCTGCGGGGC

TGCTTCCCCGCGTCCTCCGGGCCCGGGCCGCCCTCCTCCCGCACAGTGCGGAGCAGGGAGGCCCCGCGCC

TCGACCACCCGCGCCCGAGCGTCCGCGCCTCCTCCTCCGCTCTGCAGGCGGGGACCGCCCGGCGCTCGGC

ACCCGGCAGCGCGGCCCCCTCCAGCCCCCGGCTCCCGGCAGCAGAAGCAGAAGGCAGCGCCAGGGGCCGC

CGCCGCCGCCGAGCTCCGCGGGGCTCGGGAGCCGGCCCCGGCGAGGAGGCGCGGAACCATGGCCGATGGG

GGCGAGGGCGAAGACGAGATCCAGTTCCTGCGAACTGATGATGAAGTGGTTCTGCAGTGCACCGCAACCA

TCCACAAAGAACAACAGAAGCTATGCTTGGCAGCAGAAGGATTTGGCAACAGACTTTGTTTCTTGGAGTC

CACTTCCAATTCCAAGAATGTGCCCCCAGACCTCTCCATCTGCACCTTTGTGCTGGAGCAGTCCCTCTCT

GTCCGGGCGCTGCAGGAGATGCTGGCTAACACCGTGGAGAAATCAGAAGGGCAAGTTGATGTGGAAAAAT

GGAAATTCATGATGAAGACTGCTCAAGGTGGTGGTCATCGAACACTCCTCTACGGACATGCCATATTGCT

GCGCCATTCCTATAGTGGCATGTATCTGTGCTGCCTGTCCACCTCCCGGTCTTCAACTGATAAGCTGGCT

TTTGATGTTGGCTTGCAAGAGGACACCACAGGGGAGGCTTGTTGGTGGACCATACACCCTGCCTCTAAGC

AGCGATCAGAAGGAGAAAAAGTACGAGTTGGAGATGACCTCATCTTAGTTAGCGTGTCCTCTGAAAGGTA

CTTGCACTTGTCTTATGGCAACGGCAGCTTACACGTGGATGCCGCTTTCCAGCAGACTCTCTGGAGCGTG

GCCCCAATCAGCTCAGGAAGTGAGGCAGCCCAAGGGTATCTCATTGGTGGTGATGTCCTCAGGTTGCTGC

ATGGACACATGGACGAGTGTCTCACTGTCCCTTCAGGAGAACATGGTGAAGAGCAGCGGAGAACTGTTCA

TTATGAAGGTGGCGCTGTGTCTGTTCATGCACGTTCCCTTTGGAGACTAGAGACGCTAAGAGTTGCGTGG

AGTGGAAGCCACATAAGATGGGGACAGCCATTCCGACTACGCCATGTCACAACAGGAAAATACTTGAGTC

TCATGGAAGACAAAAACCTTCTACTCATGGACAAAGAGAAAGCTGATGTAAAATCAACAGCATTTACCTT

CCGGTCTTCCAAGGAAAAATTGGATGTAGGGGTGAGAAAAGAAGTAGATGGCATGGGAACATCTGAAATA

AAATACGGTGACTCAGTATGCTATATACAACATGTAGACACAGGCCTATGGCTTACTTACCAGTCTGTGG

ACGTGAAATCCGTGAGAATGGGATCTATACAACGTAAGGCTATTATGCATCATGAAGGCCACATGGATGA

TGGCATAAGTTTGTCGAGATCCCAGCATGAAGAATCACGCACAGCCCGAGTTATCCGGAGCACAGTCTTC

CTTTTCAATAGATTTATAAGGGGCCTTGATGCTCTCAGCAAGAAAGCGAAGGCTTCCACAGTCGATTTGC

CTATAGAGTCCGTAAGCCTAAGTCTGCAGGATCTCATTGGCTACTTCCACCCCCCAGATGAGCATTTAGA

GCATGAAGACAAACAGAACAGACTACGAGCCCTGAAGAATCGGCAAAATCTCTTCCAGGAAGAGGGAATG

ATCAACCTCGTGCTTGAGTGCATAGACCGTTTGCACGTCTACAGCAGTGCAGCACACTTTGCTGATGTTG

CTGGGCGAGAAGCAGGAGAGTCTTGGAAATCCATTCTGAATTCTCTGTATGAGTTGCTGGCGGCTCTAAT

TAGAGGAAATCGTAAAAACTGTGCTCAATTTTCTGGCTCCCTCGACTGGTTGATCAGCAGATTGGAAAGA

CTGGAAGCTTCTTCAGGCATTCTGGAAGTTTTACACTGTGTTTTAGTAGAAAGTCCAGAAGCTCTAAATA

TTATTAAAGAAGGACATATTAAATCTATTATCTCACTTTTAGACAAACATGGAAGAAATCACAAGGTTCT

GGATGTCTTGTGCTCACTCTGTGTTTGCCACGGGGTTGCAGTCCGTTCTAACCAGCATCTCATCTGTGAC

AATCTCCTACCAGGAAGAGACTTGTTATTGCAGACACGTCTTGTGAACCATGTCAGCAGCATGAGACCCA

ATATTTTTCTGGGCGTCAGTGAAGGTTCTGCTCAGTATAAGAAATGGTACTATGAATTGATGGTGGACCA

CACAGAGCCCTTTGTGACAGCTGAAGCAACTCACCTGCGAGTGGGCTGGGCTTCCACTGAAGGATATTCT

CCCTACCCTGGAGGGGGCGAAGAGTGGGGTGGAAATGGTGTTGGAGATGATCTCTTCTCCTATGGATTTG

ATGGCCTTCATCTCTGGTCAGGTTGTATTGCTCGTACTGTAAGCTCACCAAACCAACATCTGTTAAGAAC

TGATGATGTCATCAGTTGCTGTTTAGATCTGAGTGCCCCAAGCATCTCGTTCCGAATTAATGGACAACCT

GTTCAAGGAATGTTTGAGAATTTCAACATCGATGGCCTCTTCTTTCCAGTCGTTAGTTTCTCTGCAGGAA

TAAAAGTACGCTTTCTGCTTGGAGGGCGACATGGAGAATTCAAATTTCTTCCTCCACCTGGGTATGCTCC

TTGTTATGAAGCTGTTCTGCCAAAAGAAAAGTTGAAAGTGGAACACAGCCGAGAGTACAAGCAAGAAAGA

ACTTACACACGCGACCTGCTGGGCCCCACAGTTTCCCTGACGCAAGCTGCCTTCACACCCATCCCTGTGG

ATACCAGCCAGATCGTGTTGCCTCCTCATCTAGAAAGAATAAGAGAAAAACTGGCAGAGAATATCCATGA

ACTCTGGGTTATGAATAAAATTGAGCTTGGCTGGCAGTATGGTCCGGTTAGAGATGACAACAAGAGACAA

CACCCATGCCTGGTGGAGTTCTCCAAGCTGCCTGAACAGGAGCGCAATTACAACTTACAAATGTCGCTTG

AGACCCTGAAGACTTTGTTGGCATTAGGATGTCATGTGGGTATATCAGATGAACATGCTGAAGACAAGGT

GAAAAAAATGAAGCTACCCAAGAATTACCAGCTGACAAGTGGATACAAGCCTGCCCCTATGGACCTGAGC

TTTATCAAACTCACCCCATCACAAGAAGCAATGGTGGACAAGTTGGCAGAAAATGCACATAATGTGTGGG

CGCGGGATCGAATCCGGCAGGGCTGGACTTATGGCATCCAACAGGACGTAAAGAACAGAAGAAATCCTCG

CCTTGTTCCCTACACTCTTCTGGATGACCGAACCAAGAAATCCAACAAGGACAGCCTCCGCGAGGCTGTG

CGCACGCTGCTGGGGTACGGCTACAACTTGGAAGCACCAGATCAAGATCATGCAGCCAGAGCCGAAGTGT

GCAGCGGCACCGGGGAAAGGTTCCGAATCTTCCGTGCCGAGAAGACCTATGCAGTGAAGGCCGGACGGTG

GTATTTTGAATTTGAGACGGTCACTGCTGGAGACATGAGGGTTGGTTGGAGTCGTCCTGGTTGTCAACCG

GATCAGGAGCTTGGCTCAGATGAACGTGCCTTTGCCTTTGATGGCTTCAAGGCCCAGCGGTGGCATCAGG

GCAATGAACACTATGGGCGCTCTTGGCAAGCAGGCGATGTCGTGGGGTGTATGGTTGACATGAACGAACA

CACCATGATGTTCACACTGAATGGTGAAATCCTTCTTGATGATTCAGGCTCAGAACTGGCTTTCAAGGAC

TTTGATGTTGGCGATGGATTCATACCTGTGTGTAGCCTTGGAGTGGCTCAAGTGGGTAGGATGAACTTTG

GAAAGGATGTCAGCACCTTGAAATATTTCACCATCTGTGGCTTACAAGAGGGCTATGAACCATTTGCCGT

TAATACAAACAGGGATATTACCATGTGGCTGAGCAAGAGGCTTCCTCAGTTTCTTCAAGTTCCATCAAAC

CATGAACATATAGAGGTGACCAGAATAGACGGCACCATAGACAGTTCCCCATGTTTAAAGGTCACTCAGA

AGTCTTTTGGTTCTCAGAACAGCAACACTGATATCATGTTTTATCGCCTGAGCATGCCGATCGAGTGCGC

GGAGGTCTTCTCCAAGACGGTGGCTGGAGGGCTCCCTGGGGCTGGCCTTTTTGGGCCCAAGAATGACTTG

GAAGATTATGATGCTGATTCTGACTTTGAGGTTCTGATGAAGACAGCTCATGGCCATCTAGTGCCCGATC

GTGTTGACAAAGACAAAGAAGCTACTAAACCAGAGTTTAACAACCACAAAGATTATGCCCAGGAAAAGCC

CTCTCGTCTGAAACAAAGATTTTTGCTTAGAAGAACAAAGCCAGATTACAGCACAAGCCATTCTGCAAGA

CTCACCGAAGATGTCCTTGCTGATGATCGGGATGACTATGATTTCTTGATGCAAACGTCCACGTACTATT

ACTCAGTGAGAATCTTTCCTGGACAAGAACCTGCTAATGTCTGGGTGGGCTGGATTACATCAGATTTCCA

TCAGTATGACACAGGCTTTGACTTGGACAGAGTTCGCACAGTAACAGTTACTCTAGGAGATGAAAAAGGA

AAAGTGCATGAAAGCATCAAACGCAGCAACTGCTATATGGTATGTGCGGGTGAGAGCATGAGCCCCGGGC

AAGGACGCAACAATAATGGACTGGAGATTGGCTGTGTGGTGGATGCTGCCAGCGGGCTGCTCACATTCAT

TGCCAATGGCAAGGAACTGAGCACATACTATCAGGTGGAACCGAGTACAAAATTATTTCCTGCGGTTTTT

GCACAAGCTACAAGTCCCAATGTTTTCCAGTTTGAGTTGGGAAGAATAAAGAATGTGATGCCTCTCTCGG

CGGGATTATTCAAGAGTGAGCACAAGAACCCCGTGCCGCAGTGCCCCCCGCGCCTCCACGTGCAGTTCCT

GTCACACGTCCTGTGGAGCAGAATGCCCAACCAGTTTTTGAAGGTAGATGTGTCTCGAATAAGTGAACGC

CAAGGCTGGTTGGTGCAGTGTTTGGATCCTCTGCAGTTCATGTCTCTTCATATCCCTGAGGAAAACAGAT

CTGTTGACATCTTAGAGTTGACAGAGCAGGAGGAATTGCTGAAATTTCACTATCACACTCTCCGGCTCTA

CTCAGCCGTCTGTGCTCTTGGGAACCACCGGGTGGCCCATGCCCTGTGCAGCCATGTGGATGAACCTCAG

CTCCTCTATGCCATTGAGAACAAGTACATGCCTGGTTTGCTGCGTGCTGGCTACTATGACCTGCTGATTG

ACATCCACCTGAGCTCCTATGCCACTGCCAGGCTCATGATGAACAACGAGTACATTGTCCCCATGACGGA

GGAGACGAAGAGCATCACCCTGTTCCCTGATGAGAACAAAAAACACGGCCTTCCAGGGATCGGCCTCAGC

ACCTCCCTCAGGCCACGGATGCAGTTTTCCTCCCCCAGTTTTGTAAGCATTAGTAATGAATGTTACCAGT

ACAGTCCAGAGTTCCCACTGGACATCCTCAAGTCCAAAACCATACAGATGCTGACAGAAGCTGTTAAAGA

GGGCAGTCTTCATGCCCGGGACCCAGTTGGAGGGACTACTGAATTCCTCTTTGTACCTCTCATCAAGCTT

TTCTATACCCTGCTGATCATGGGCATCTTTCACAACGAGGACTTGAAGCACATCTTGCAGTTGATTGAGC

CCAGTGTGTTTAAAGAAGCTGCCACTCCGGAGGAGGAGAGTGACACGCTGGAGAAAGAGCTCAGTGTGGA

CGATGCAAAGCTGCAAGGAGCTGGTGAGGAAGAAGCCAAGGGGGGCAAGCGGCCCAAGGAAGGCCTGCTC

CAAATGAAACTGCCAGAGCCAGTTAAATTGCAGATGTGCCTACTGCTTCAGTACCTCTGTGACTGCCAGG

TCCGGCACCGGATAGAAGCCATTGTAGCCTTTTCAGATGATTTTGTGGCTAAGCTCCAAGACAATCAACG

TTTCCGATACAACGAAGTCATGCAAGCCTTAAACATGTCAGCTGCACTCACAGCCAGGAAGACAAAGGAA

TTTAGATCACCACCTCAAGAACAGATCAATATGCTTCTCAATTTTAAGGATGACAAAAGTGAATGTCCAT

GTCCAGAAGAAATTCGTGACCAACTATTGGATTTCCATGAAGATTTGATGACACATTGTGGAATTGAGCT

GGATGAAGATGGGTCTCTGGATGGAAACAGTGATTTAACAATTAGAGGGCGTCTGCTATCCCTGGTAGAA

AAGGTGACATATCTGAAGAAGAAGCAAGCAGAAAAACCAGTTGAGAGTGACTCCAAAAAGTCCTCCACTC

TGCAGCAGCTGATTTCTGAGACCATGGTCCGATGGGCTCAGGAGTCTGTCATTGAAGACCCCGAGCTGGT

GAGGGCCATGTTTGTGTTGCTCCATCGGCAGTATGACGGCATTGGGGGTCTTGTTCGGGCCCTGCCAAAG

ACCTACACGATAAATGGTGTGTCCGTGGAGGACACCATCAACCTGCTGGCATCCCTTGGTCAGATTCGGT

CCCTGCTGAGTGTGAGAATGGGCAAAGAAGAAGAGAAGCTCATGATTCGTGGATTAGGGGATATTATGAA

TAACAAAGTGTTTTACCAGCACCCTAATCTCATGAGGGCACTGGGGATGCACGAGACTGTGATGGAGGTC

ATGGTGAACGTCCTTGGAGGTGGAGAGTCCAAGGAAATCACCTTTCCCAAGATGGTGGCCAACTGTTGCC

GTTTTCTCTGTTACTTCTGTCGTATAAGTAGGCAGAATCAAAAAGCTATGTTTGATCATCTCAGTTATTT

ACTGGAAAACAGCAGTGTTGGTCTTGCCTCCCCAGCTATGAGAGGTTCAACACCACTGGATGTGGCTGCA

GCTTCGGTGATGGATAATAATGAACTAGCATTAGCTCTGCGTGAGCCGGATCTAGAAAAGGTAGTTCGTT

ATTTGGCTGGTTGTGGACTGCAAAGTTGCCAGATGCTGGTGTCTAAGGGCTATCCAGACATTGGGTGGAA

CCCAGTTGAAGGAGAGAGATATCTTGACTTTCTTAGATTTGCTGTCTTCTGTAATGGGGAGAGTGTGGAG

GAAAATGCAAATGTCGTGGTGAGATTGCTCATTCGGAGGCCTGAGTGTTTTGGTCCTGCTTTGAGAGGAG

AAGGTGGGAATGGGCTTCTTGCAGCAATGGAAGAAGCCATCAAAATCGCCGAGGATCCTTCCCGAGATGG

TCCCTCACCAAATAGCGGATCCAGTAAAACACTTGACACAGAGGAGGAGGAAGATGACACTATCCACATG

GGGAACGCGATCATGACCTTCTATTCAGCTTTGATTGACCTCTTGGGACGCTGTGCTCCTGAGATGCATT

TGATTCATGCCGGGAAGGGAGAAGCCATCAGAATTAGGTCCATTTTGAGATCCCTCATTCCCCTGGGAGA

TTTGGTGGGCGTTATCAGCATCGCTTTTCAGATGCCAACAATAGCCAAAGATGGGAATGTGGTGGAACCT

GACATGTCTGCGGGGTTTTGCCCAGATCACAAGGCAGCCATGGTTTTATTCCTTGACAGGGTCTATGGGA

TTGAGGTTCAAGACTTCCTCCTCCATCTTCTTGAGGTTGGCTTTCTGCCAGATCTCCGGGCGGCTGCTTC

TTTAGATACGGCAGCTTTGAGTGCTACAGACATGGCCTTGGCCCTCAATCGGTACCTTTGCACAGCCGTC

TTGCCATTGTTAACAAGATGTGCTCCTCTCTTTGCTGGCACAGAGCACCACGCTTCTCTCATTGACTCAT

TACTTCATACTGTGTATAGACTTTCTAAGGGCTGTTCACTTACCAAAGCTCAGCGGGATTCCATAGAAGT

TTGTTTACTCTCTATTTGTGGACAACTGAGACCTTCTATGATGCAGCACTTACTCAGAAGATTAGTATTT

GATGTTCCATTATTAAATGAACACGCAAAGATGCCTCTTAAACTGCTGACAAATCATTATGAAAGATGCT

GGAAATATTACTGCCTGCCTGGAGGGTGGGGAAACTTTGGTGCTGCCTCAGAAGAAGAACTTCATTTATC

7. Motif

Pfam (6 motifs)

Pfam	Position(Independent E-value)	Description
RYDR_Jsol	1654..2090(2.8e-198)	PF21119, Ryanodine receptor junctional solenoid repeat
RYDR_ITPR	455..648(1.2e-73) 2124..2335(7.6e-59)	PF01365, RIH domain
RyR	862..950(5.8e-33) 976..1065(1.6e-30) 2701..2791(4.8e-33) 2821..2904(3.7e-25)	PF02026, RyR domain
SPRY	672..806(6.6e-22) 1100..1219(8.6e-26) 1426..1559(6.4e-21)	PF00622, SPRY domain
Ins145_P3_rec	10..222(1.7e-65)	PF08709, Inositol 1,4,5-trisphosphate/ryanodine receptor
MIR	226..405(8.6e-64)	PF02815, MIR 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 (-17313.22) 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 5274 positions in the final dataset.

9. SNP

SNP	COORDINATE	AMINO ACID CHANGE	GENE ID	TRANSCRIPT ID	PROTEIN ID	SIFT SCORE	SIFT MEDIAN	SIFT PREDICTION
rs121918597	237798237	S2244L	ENSG00000198626	ENST00000360064	ENSP00000353174
rs121918597	237798237	S2246L	ENSG00000198626	ENST00000366574	ENSP00000355533
rs121918597	237798237	S2230L	ENSG00000198626	ENST00000542537	ENSP00000443798	0	2.3	DELETERIOUS
rs121918598	237811823	R2472S	ENSG00000198626	ENST00000360064	ENSP00000353174	0	2.39	DELETERIOUS
rs121918598	237811823	R2474S	ENSG00000198626	ENST00000366574	ENSP00000355533	0	2.3	DELETERIOUS
rs121918598	237811823	R2458S	ENSG00000198626	ENST00000542537	ENSP00000443798
rs121918599	237947324	N4110K	ENSG00000198626	ENST00000360064	ENSP00000353174
rs121918599	237947324	N4104K	ENSG00000198626	ENST00000366574	ENSP00000355533
rs121918599	237947324	N4088K	ENSG00000198626	ENST00000542537	ENSP00000443798
rs121918600	237954741	R4503C	ENSG00000198626	ENST00000360064	ENSP00000353174
rs121918600	237954741	R4497C	ENSG00000198626	ENST00000366574	ENSP00000355533
rs121918600	237954741	R4481C	ENSG00000198626	ENST00000542537	ENSP00000443798	0	2.3	DELETERIOUS
rs121918601	237804238	N2384I	ENSG00000198626	ENST00000360064	ENSP00000353174	0	2.39	DELETERIOUS
rs121918601	237804238	N2386I	ENSG00000198626	ENST00000366574	ENSP00000355533	0	2.3	DELETERIOUS
rs121918601	237804238	N2370I	ENSG00000198626	ENST00000542537	ENSP00000443798	0	2.39	DELETERIOUS
rs121918602	237617696	L431P	ENSG00000198626	ENST00000360064	ENSP00000353174
rs121918602	237617696	L433P	ENSG00000198626	ENST00000366574	ENSP00000355533
rs121918602	237617696	L417P	ENSG00000198626	ENST00000542537	ENSP00000443798
rs121918603	237802368	P2326S	ENSG00000198626	ENST00000360064	ENSP00000353174
rs121918603	237802368	P2328S	ENSG00000198626	ENST00000366574	ENSP00000355533
rs121918603	237802368	P2312S	ENSG00000198626	ENST00000542537	ENSP00000443798
rs121918605	237947614	Q4207R	ENSG00000198626	ENST00000360064	ENSP00000353174
rs121918605	237947614	Q4201R	ENSG00000198626	ENST00000366574	ENSP00000355533
rs121918605	237947614	Q4185R	ENSG00000198626	ENST00000542537	ENSP00000443798
rs121918606	237982481	A4866G	ENSG00000198626	ENST00000360064	ENSP00000353174
rs121918606	237982481	A4860G	ENSG00000198626	ENST00000366574	ENSP00000355533
rs121918606	237982481	A4844G	ENSG00000198626	ENST00000542537	ENSP00000443798
rs190140598	237608788	R418W	ENSG00000198626	ENST00000360064	ENSP00000353174
rs190140598	237608788	R420W	ENSG00000198626	ENST00000366574	ENSP00000355533	0	2.3	DELETERIOUS
rs190140598	237608788	R404W	ENSG00000198626	ENST00000542537	ENSP00000443798	0	2.39	DELETERIOUS
rs200236750	237729972	T1105M	ENSG00000198626	ENST00000360064	ENSP00000353174	0	2.3	DELETERIOUS
rs200236750	237729972	T1107M	ENSG00000198626	ENST00000366574	ENSP00000355533	0	2.39	DELETERIOUS
rs200236750	237729972	T1091M	ENSG00000198626	ENST00000542537	ENSP00000443798	0	2.3	DELETERIOUS

Evolutionary analysis of coding SNPs

SNP	Substitution	Probability of deleterious effect	Prediction Score
rs121918597	S2246L	probably damaging	0.85
rs121918598	R2474S	probably damaging	0.85
rs121918601	N2386I	probably damaging	0.74
rs121918602	L433P	probably damaging	0.74
rs121918603	P2328S	probably damaging	0.85
rs190140598	R420W	probably damaging	0.85
rs200236750	T1107M	probably benign	0.19

Provean

SNP Id’s	Amino Acid Change	Probability	Prediction	Score
rs121918597	S2244L	Deleterious	Damaging	-5.05
rs121918597	S2246L	Deleterious	Damaging	-5.05
rs121918597	S2230L	Deleterious	Damaging	-5.05
rs121918598	R2472S	Deleterious	Damaging	-5.22
rs121918598	R2474S	Deleterious	Damaging	-5.22
rs121918598	R2458S	Deleterious	Damaging	-5.22
rs121918599	N4110K	Deleterious	Damaging	-4.93
rs121918599	N4104K	Deleterious	Damaging	-4.93
rs121918599	N4088K	Deleterious	Damaging	-4.93
rs121918600	R4503C	Deleterious	Damaging	-7.06
rs121918600	R4497C	Deleterious	Damaging	-7.06
rs121918600	R4481C	Deleterious	Damaging	-7.06
rs121918601	N2384I	Deleterious	Damaging	-6.46
rs121918601	N2386I	Deleterious	Damaging	-6.46
rs121918601	N2370I	Deleterious	Damaging	-6.46
rs121918602	L431P	Deleterious	Damaging	-4
rs121918602	L433P	Deleterious	Damaging	-4
rs121918602	L417P	Deleterious	Damaging	-4
rs121918603	P2326S	Deleterious	Damaging	-7.32
rs121918603	P2328S	Deleterious	Damaging	-7.32
rs121918603	P2312S	Deleterious	Damaging	-7.32
rs121918605	Q4207R	Deleterious	Damaging	-3.26
rs121918605	Q4201R	Deleterious	Damaging	-3.26
rs121918605	Q4185R	Deleterious	Damaging	-3.26
rs121918606	A4866G	Deleterious	Damaging	-3.33
rs121918606	A4860G	Deleterious	Damaging	-3.33
rs121918606	A4844G	Deleterious	Damaging	-3.33
rs190140598	R418W	Deleterious	Damaging	-4.15
rs190140598	R420W	Deleterious	Damaging	-4.15
rs190140598	R404W	Deleterious	Damaging	-4.15
rs200236750	T1105M	Neutral	Damaging	-0.54
rs200236750	T1107M	Neutral	Damaging	-0.54
rs200236750	T1091M	Neutral	Damaging	-0.54

SNAP 2

Wildetype Amino Acid	Position	Variant Amino Acid	Predicted Effect	Score	Expected Accurancy
S	2244	L	Effect	77	80%
S	2246	L	Neutral	65	56%
S	2230	L	Effect	35	35%
R	2472	S	Neutral	87	96%
R	2474	S	Effect	-40	75%
R	2458	S	Effect	64	26%
N	4110	K	Neutral	90	34%
N	4104	K	Effect	39	85%
N	4088	K	Effect	73	26%
R	4503	C	Neutral	96	34%
R	4497	C	Neutral	35	85%
R	4481	C	Effect	15	75%
N	2384	I	Neutral	-29	95%
N	2386	I	Neutral	57	26%
N	2370	I	Neutral	56	48%
L	431	P	Effect	66	56%
L	433	P	Effect	33	80%
L	417	P	Effect	26	90%
P	2326	S	Neutral	85	56%
P	2328	S	Neutral	56	26%
P	2312	S	Effect	65	88%
Q	4207	R	Effect	45	98%
Q	4201	R	Effect	26	99%
Q	4185	R	Neutral	26	56%
A	4866	G	Neutral	-52	49%
A	4860	G	Neutral	96	79%
A	4844	G	Effect	79	59%
R	418	W	Effect	96	90%
R	420	W	Effect	56	79%
R	404	W	Neutral	25	74%
T	1105	M	Neutral	36	46%
T	1107	M	Neutral	24	58%
T	1091	M	Effect	75	49%

Polyphen 2

Rs_Id	Mutation Probability	Score
rs121918597	Probably damaging	0.98
rs121918597	Possibly damaging	0.98
rs121918597	Possibly damaging	1.00
rs121918598	Possibly damaging	0.98
rs121918598	Probably damaging	0.98
rs121918598	Possibly damaging	0.98
rs121918599	Possibly damaging	1.00
rs121918599	Possibly damaging	0 .98
rs121918599	Possibly damaging	1.00
rs121918600	Possibly damaging	0.98
rs121918600	Possibly damaging	1.00
rs121918600	Possibly damaging	0.98
rs121918601	Possibly damaging	1.00
rs121918601	Possibly damaging	1.00
rs121918601	Possibly damaging	0.98
rs121918602	Possibly damaging	1.00
rs121918602	Possibly damaging	0.98
rs121918602	Possibly damaging	1.00
rs121918603	Probably damaging	0.98
rs121918603	Possibly damaging	0.98
rs121918603	Possibly damaging	1.00
rs121918605	Possibly damaging	0.98
rs121918605	Possibly damaging	1.00
rs121918605	Possibly damaging	0.98
rs121918606	Possibly damaging	1.00
rs121918606	Possibly damaging	0.98
rs121918606	Possibly damaging	1.00
rs190140598	Possibly damaging	1.00
rs190140598	Possibly damaging	0.98
rs190140598	Possibly damaging	1.00
rs200236750	Possibly damaging	0.98
rs200236750	Possibly damaging	1.00
rs200236750	Possibly damaging	1.00
rs121918597	Probably damaging	0.98
rs121918597	Possibly damaging	0.98
rs121918597	Possibly damaging	1.00
rs121918598	Possibly damaging	0.98
rs121918598	Possibly damaging	1.00

Hope Prediction

Rs_Ids	Mutation	Mapping Issues	AA Variant	Function Impact	Score
rs121918597	RYR2_S2244L		S2244L	High	10.2
rs121918597	RYR2_S2246L	Uniprot Residue:H	S2246L	Medium	4.85
rs121918597	RYR2_S2230L		S2230L	Medium	3.52
rs121918598	RYR2_R2472S		R2472S	High	6.94
rs121918598	RYR2_R2474S		R2474S	High	9.8
rs121918598	RYR2_R2458S	Uniprot Residue:I	R2458S	High	6.51
rs121918599	RYR2_N4110K		N4110K	Medium	3.66
rs121918599	RYR2_N4104K		N4104K	Medium	4.2
rs121918599	RYR2_N4088K		N4088K	Low	0.71
rs121918600	RYR2_R4503C	Uniprot Residue:M	R4503C	Medium	5.28
rs121918600	RYR2_R4497C		R4497C	High	10.5
rs121918600	RYR2_R4481C		R4481C	Medium	4.82
rs121918601	RYR2_N2384I		N2384I	Medium	4.56
rs121918601	RYR2_N2386I		N2386I	High	5.94
rs121918601	RYR2_N2370I	Uniprot Residue:C	N2370I	High	10.6
rs121918602	RYR2_L431P		L431P	High	6.23
rs121918602	RYR2_L433P		L433P	Medium	3.55
rs121918602	RYR2_L417P		L417P	Medium	4.3
rs121918603	RYR2_P2326S		P2326S	Low	0.22
rs121918603	RYR2_P2328S	Uniprot Residue:L	P2328S	High	6.33
rs121918603	RYR2_P2312S		P2312S	Medium	4.12
rs121918605	RYR2_Q4207R		Q4207R	Medium	4.3
rs121918605	RYR2_Q4201R		Q4201R	Low	0.82
rs121918605	RYR2_Q4185R		Q4185R	Medium	5.23
rs121918606	RYR2_A4866G	Uniprot Residue:V	A4866G	Medium	5.23
rs121918606	RYR2_A4860G		A4860G	Medium	2.62
rs121918606	RYR2_A4844G		A4844G	Medium	2.62
rs190140598	RYR2_R418W		R418W	Low	1.59
rs190140598	RYR2_R420W		R420W	Medium	2.16
rs190140598	RYR2_R404W		R404W	Medium	2.16
rs200236750	RYR2_T1105M		T1105M	High	6.62
rs200236750	RYR2_T1107M		T1107M	High	6.62
rs200236750	RYR2_T1091M	Uniprot Residue:G	T1091M	Medium	2.16

10. Active Site

Rank	C-Score	Cluster Size	PDB Hit	Lig Name	Consensus Building Residues
1	0.04	3	3i8hE	MG	428,431
2	0.03	2	3uj0A	I3P	258,260,261,262,490,544, 545,546
3	0.03	2	3cmvC	ANP	129,131,132,133,141
4	0.03	2	2vd9A	MG	229,232
5	0.03	2	2z48A	NGA	232,277,343,359,404,405
6	0.03	2	2fqqA	F1G	149,169
7	0.02	1	N/A	N/A	527,534,535,538,566,569, 573,577,581,609,613
8	0.02	1	N/A	N/A	58,62,276,278
9	0.02	1	N/A	N/A	249,269,270,271,272,301,302, 416,419,484,488,491,492,495, 496,499,537,540,541,543,544, 546,547,550,551,554,557,558, 561,574,578
10	0.01	1	N/A	N/A	415,418,462,463,485,486,489

11. Primary Sequence Analysis

Number of amino acids

3705

Molecular weight

419261.48

Theoretical pI

6.01

Amino acid composition

Ala (A) 240 6.5%

Arg (R) 208 5.6%

Asn (N) 142 3.8%

Asp (D) 207 5.6%

Cys (C) 75 2.0%

Gln (Q) 140 3.8%

Glu (E) 288 7.8%

Gly (G) 232 6.3%

His (H) 120 3.2%

Ile (I) 172 4.6%

Leu (L) 426 11.5%

Lys (K) 219 5.9%

Met (M) 111 3.0%

Phe (F) 144 3.9%

Pro (P) 158 4.3%

Ser (S) 270 7.3%

Thr (T) 163 4.4%

Trp (W) 46 1.2%

Tyr (Y) 119 3.2%

Val (V) 225 6.1%

Pyl (O) 0 0.0%

Sec (U) 0 0.0%

Total number of negatively charged residues (Asp + Glu)

495

Total number of positively charged residues (Arg + Lys)

427

Formula

C₁₈₆₂₀H₂₉₂₈₆N₅₁₁₆O₅₅₃₀S₁₈₆₀

Total number of atoms(12269)

58738

Instability index(II)

45.95

Stability

Unstable

Aliphatic index(AI)

87.04

GRAVY

-0.322

12. Secondary structure analysis

Alpha helix (Hh) : 1705 is 46.02%

310 helix (Gg) : 0 is 0.00%

Pi helix (Ii) : 0 is 0.00%

Beta bridge (Bb) : 0 is 0.00%

Extended strand (Ee) : 495 is 13.36%

Beta turn (Tt) : 196 is 5.29%

Bend region (Ss) : 0 is 0.00%

Random coil (Cc) : 1309 is 35.33%

Ambiguous states (?) : 0 is 0.00%

Other states : 0 is 0.00%

Secondary Structure Prediction

Amino Acid Types

13. Enzymes

Name of enzyme	No. of cleavages
Arg-C proteinase	208
Asp-N endopeptidase	207
Asp-N endopeptidase + N-terminal Glu	495
BNPS-Skatole	46
CNBr	111
Chymotrypsin-high specificity (C-term to [FYW], not before P)	296
Chymotrypsin-low specificity (C-term to [FYWML], not before P)	908
Clostripain	208
Formic acid	207
Glutamyl endopeptidase	288
Iodosobenzoic acid	46
Hydroxylamine	11
Iodosobenzoic acid	45
LysC	89
LysN	49
NTCB (2-nitro-5-thiocyanobenzoic acid)	88
Pepsin (pH1.3)	786
Pepsin (pH>2)	971
Proline-endopeptidase	20
Proteinase K	1823
Staphylococcal peptidase I	259
Thermolysin	1094
Trypsin	411

14. Epitope

Rank	Start position	Sequence	Score	Prediction
1	136	SRSSTDKLAFDVGLQE	0.97	Epitope
2	286	GSHIRWGQPFRLRHVT	0.94	Epitope
3	900	LGWQYGPVRDDNKRQH	0.93	Epitope
4	1079	SGTGERFRIFRAEKTY	0.92	Epitope
4	1015	GWTYGIQQDVKNRRNP	0.92	Epitope
5	232	DVLRLLHGHMDECLTV	0.91	Epitope
5	1186	SGSELAFKDFDVGDGF	0.91	Epitope
6	33	QKLCLAAEGFGNRLCF	0.90	Epitope
6	252	HGEEQRRTVHYEGGAV	0.90	Epitope
6	1274	DGTIDSSPCLKVTQKS	0.90	Epitope
6	1229	ICGLQEGYEPFAVNTN	0.90	Epitope
7	692	HLRVGWASTEGYSPYP	0.89	Epitope
7	629	QHLICDNLLPGRDLLL	0.89	Epitope
7	1284	KVTQKSFGSQNSNTDI	0.89	Epitope
8	4	GGEGEDEIQFLRTDDE	0.88	Epitope
8	1109	TAGDMRVGWSRPGCQP	0.88	Epitope
9	983	LSFIKLTPSQEAMVDK	0.87	Epitope
9	738	ARTVSSPNQHLLRTDD	0.87	Epitope
9	463	FHPPDEHLEHEDKQNR	0.87	Epitope
9	353	EIKYGDSVCYIQHVDT	0.87	Epitope

15. Protein-Protein Interaction

No of Nodes	11
No of Edges	31
Avg node degree	5.64
avg. local clustering coefficient	0.801
expected number of e, dges	11
p-value	7.51e-07
Protein – Protein Interaction network

16. MRNA

RNA Base Pairing Probability Plot