In Silico Analysis of Novel Titin Non-Synonymous Missense Variants Detected by Targeted Next-Generation Sequencing in a Cohort of Romanian Index Patients with Hypertrophic Cardiomyopathy

1 Granzier HL, Irving TC. Passive tension in cardiac muscle: contribution of collagen, titin, microtubules, and intermediate filaments. Biophys J 1995;68 [DOI: 10.1016/S0006-3495(95)80278-X] GranzierHL IrvingTC Passive tension in cardiac muscle: contribution of collagen, titin, microtubules, and intermediate filaments Biophys J 1995 68 10.1016/S0006-3495(95)80278-X Open DOISearch in Google Scholar

2 Cazorla O, Wu Y, Irving TC, Granzier H. Titin-based modulation of calcium sensitivity of active tension in mouse skinned cardiac myocytes. Circ Res 2001;88 [DOI: 10.1161/hh1001.090876] CazorlaO WuY IrvingTC GranzierH Titin-based modulation of calcium sensitivity of active tension in mouse skinned cardiac myocytes Circ Res 2001 88 10.1161/hh1001.090876 11375272 Open DOISearch in Google Scholar

3 Kontrogianni-Konstantopoulos A, Ackermann MA, Bowman AL, Yap S V., Bloch RJ. Muscle giants: Molecular scaffolds in sarcomerogenesis. Physiol. Rev. 2009;89 [DOI: 10.1152/physrev.00017.2009] Kontrogianni-KonstantopoulosA AckermannMA BowmanAL YapS V BlochRJ Muscle giants: Molecular scaffolds in sarcomerogenesis Physiol. Rev. 2009 89 10.1152/physrev.00017.2009 307673319789381 Open DOISearch in Google Scholar

4 Akinrinade O, Koskenvuo JW, Alastalo TP. Prevalence of titin truncating variants in general population. PLoS One 2015;10 [DOI: 10.1371/journal.pone.0145284] AkinrinadeO KoskenvuoJW AlastaloTP Prevalence of titin truncating variants in general population PLoS One 2015 10 10.1371/journal.pone.0145284 468940326701604 Open DOISearch in Google Scholar

5 Roberts AM, Ware JS, Herman DS, Schafer S, Baksi J, Bick AG, Buchan RJ, Walsh R, John S, Wilkinson S, Mazzarotto F, Felkin LE, Gong S, Macarthur JAL, Cunningham F, Flannick J, Gabriel SB, Altshuler DM, MacDonald PS, Heinig M, Keogh AM, Hayward CS, Banner NR, Pennell DJ, O’Regan DP, San TR, De Marvao A, Dawes TJW, Gulati A, Birks EJ, Yacoub MH, Radke M, Gotthardt M, Wilson JG, O’Donnell CJ, Prasad SK, Barton PJR, Fatkin D, Hubner N, Seidman JG, Seidman CE, Cook SA. Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease. Sci Transl Med 2015;7 [DOI: 10.1126/scitranslmed.3010134] RobertsAM WareJS HermanDS SchaferS BaksiJ BickAG BuchanRJ WalshR JohnS WilkinsonS MazzarottoF FelkinLE GongS MacarthurJAL CunninghamF FlannickJ GabrielSB AltshulerDM MacDonaldPS HeinigM KeoghAM HaywardCS BannerNR PennellDJ O’ReganDP SanTR De MarvaoA DawesTJW GulatiA BirksEJ YacoubMH RadkeM GotthardtM WilsonJG O’DonnellCJ PrasadSK BartonPJR FatkinD HubnerN SeidmanJG SeidmanCE CookSA Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease Sci Transl Med 2015 7 10.1126/scitranslmed.3010134 456009225589632 Open DOISearch in Google Scholar

6 Akinrinade O, Alastalo TP, Koskenvuo JW. Relevance of truncating titin mutations in dilated cardiomyopathy. Clin Genet 2016;90 [DOI: 10.1111/cge.12741] AkinrinadeO AlastaloTP KoskenvuoJW Relevance of truncating titin mutations in dilated cardiomyopathy Clin Genet 2016 90 10.1111/cge.12741 26777568 Open DOISearch in Google Scholar

7 Akinrinade O, Heliö T, Lekanne Deprez RH, Jongbloed JDH, Boven LG, van den Berg MP, Pinto YM, Alastalo TP, Myllykangas S, Spaendonck-Zwarts K van, Tintelen JP van, van der Zwaag PA, Koskenvuo J. Relevance of Titin Missense and Non-Frameshifting Insertions/Deletions Variants in Dilated Cardiomyopathy. Sci Rep 2019;9 [DOI: 10.1038/s41598-019-39911-x] AkinrinadeO HeliöT Lekanne DeprezRH JongbloedJDH BovenLG van den BergMP PintoYM AlastaloTP MyllykangasS Spaendonck-ZwartsK van TintelenJP van van der ZwaagPA KoskenvuoJ Relevance of Titin Missense and Non-Frameshifting Insertions/Deletions Variants in Dilated Cardiomyopathy Sci Rep 2019 9 10.1038/s41598-019-39911-x 641204630858397 Open DOISearch in Google Scholar

8 van Lint FHM, Mook ORF, Alders M, Bikker H, Lekanne dit Deprez RH, Christiaans I. Large next-generation sequencing gene panels in genetic heart disease: yield of pathogenic variants and variants of unknown significance. Netherlands Hear J 2019;27 [DOI: 10.1007/s12471-019-1250-5] van LintFHM MookORF AldersM BikkerH Lekanne dit DeprezRH ChristiaansI Large next-generation sequencing gene panels in genetic heart disease: yield of pathogenic variants and variants of unknown significance Netherlands Hear J 2019 27 10.1007/s12471-019-1250-5 653334630847666 Open DOISearch in Google Scholar

9 Pottinger TD, Puckelwartz MJ, Pesce LL, Robinson A, Kearns S, Pacheco JA, Rasmussen-Torvik LJ, Smith ME, Chisholm R, McNally EM. Pathogenic and Uncertain Genetic Variants Have Clinical Cardiac Correlates in Diverse Biobank Participants. J Am Heart Assoc 2020;9 [DOI: 10.1161/JAHA.119.013808] PottingerTD PuckelwartzMJ PesceLL RobinsonA KearnsS PachecoJA Rasmussen-TorvikLJ SmithME ChisholmR McNallyEM Pathogenic and Uncertain Genetic Variants Have Clinical Cardiac Correlates in Diverse Biobank Participants J Am Heart Assoc 2020 9 10.1161/JAHA.119.013808 703389332009526 Open DOISearch in Google Scholar

10 Micheu MM, Popa-Fotea N-M, Oprescu N, Bogdan S, Dan M, Deaconu A, Dorobantu L, Gheorghe-Fronea O, Greavu M, Iorgulescu C, Scafa-Udriste A, Ticulescu R, Vatasescu RG, Dorobantu M. Yield of Rare Variants Detected by Targeted Next-Generation Sequencing in a Cohort of Romanian Index Patients with Hypertrophic Cardiomyopathy. Diagnostics 2020;10 [DOI: 10.3390/diagnostics10121061] MicheuMM Popa-FoteaN-M OprescuN BogdanS DanM DeaconuA DorobantuL Gheorghe-FroneaO GreavuM IorgulescuC Scafa-UdristeA TiculescuR VatasescuRG DorobantuM Yield of Rare Variants Detected by Targeted Next-Generation Sequencing in a Cohort of Romanian Index Patients with Hypertrophic Cardiomyopathy Diagnostics 2020 10 10.3390/diagnostics10121061 776233233297573 Open DOISearch in Google Scholar

11 Zamorano JL, Anastasakis A, Borger MA, Borggrefe M, Cecchi F, Charron P, Hagege AA, Lafont A, Limongelli G, Mahrholdt H, McKenna WJ, Mogensen J, Nihoyannopoulos P, Nistri S, Piepe PG, Pieske B, Rapezzi C, Rutten FH, Tillmanns C, Watkins H, O’Mahony C, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol Ç, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S, Alfonso F, Basso C, Cardim NM, Gimeno JR, Heymans S, Holm PJ, Keren A, Lionis C, Muneretto C, Priori S, Salvador MJ, Wolpert C. 2014 ESC guidelines on diagnosis and management of hypertrophic cardiomyopathy: The task force for the diagnosis and management of hypertrophic cardiomyopathy of the European Society of Cardiology (ESC). Eur. Heart J. 2014;35 [DOI: 10.1093/eurheartj/ehu284] ZamoranoJL AnastasakisA BorgerMA BorggrefeM CecchiF CharronP HagegeAA LafontA LimongelliG MahrholdtH McKennaWJ MogensenJ NihoyannopoulosP NistriS PiepePG PieskeB RapezziC RuttenFH TillmannsC WatkinsH O’MahonyC AchenbachS BaumgartnerH BaxJJ BuenoH DeanV DeatonC ErolÇ FagardR FerrariR HasdaiD HoesAW KirchhofP KnuutiJ KolhP LancellottiP LinhartA PiepoliMF PonikowskiP SirnesPA TamargoJL TenderaM TorbickiA WijnsW WindeckerS AlfonsoF BassoC CardimNM GimenoJR HeymansS HolmPJ KerenA LionisC MunerettoC PrioriS SalvadorMJ WolpertC 2014 ESC guidelines on diagnosis and management of hypertrophic cardiomyopathy: The task force for the diagnosis and management of hypertrophic cardiomyopathy of the European Society of Cardiology (ESC) Eur. Heart J. 2014 35 10.1093/eurheartj/ehu284 25173338 Open DOISearch in Google Scholar

12 Micheu MM, Popa-Fotea NM, Oprescu N, Dorobantu M, Ratiu AC, Ecovoiu AA. NGS data validated by Sanger sequencing reveal a puzzling small deletion of MYBPC3 gene associated with hypertrophic cardiomyopathy. Rom Biotechnol Lett 2019;24:91–9 [DOI: 10.25083/rbl/24.1/91.99] MicheuMM Popa-FoteaNM OprescuN DorobantuM RatiuAC EcovoiuAA NGS data validated by Sanger sequencing reveal a puzzling small deletion of MYBPC3 gene associated with hypertrophic cardiomyopathy Rom Biotechnol Lett 2019 24 91 9 10.25083/rbl/24.1/91.99 Open DOISearch in Google Scholar

13 Li H. [Heng Li - Compares BWA to other long read aligners like CUSHAW2] Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. arXiv Prepr arXiv 2013; LiH [Heng Li - Compares BWA to other long read aligners like CUSHAW2] Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM arXiv Prepr arXiv 2013 Search in Google Scholar

14 Semsarian C, Ingles J, Maron MS, Maron BJ. New perspectives on the prevalence of hypertrophic cardiomyopathy. J. Am. Coll. Cardiol. 2015;65 [DOI: 10.1016/j.jacc.2015.01.019] SemsarianC InglesJ MaronMS MaronBJ New perspectives on the prevalence of hypertrophic cardiomyopathy J. Am. Coll. Cardiol. 2015 65 10.1016/j.jacc.2015.01.019 25814232 Open DOISearch in Google Scholar

15 Jagadeesh KA, Wenger AM, Berger MJ, Guturu H, Stenson PD, Cooper DN, Bernstein JA, Bejerano G. M-CAP eliminates a majority of variants of uncertain significance in clinical exomes at high sensitivity. Nat Genet 2016;48 [DOI: 10.1038/ng.3703] JagadeeshKA WengerAM BergerMJ GuturuH StensonPD CooperDN BernsteinJA BejeranoG M-CAP eliminates a majority of variants of uncertain significance in clinical exomes at high sensitivity Nat Genet 2016 48 10.1038/ng.3703 27776117 Open DOISearch in Google Scholar

16 Laddach A, Gautel M, Fraternali F. TITINdb-a computational tool to assess titin's role as a disease gene. Bioinformatics 2017;33 [DOI: 10.1093/bioinformatics/btx424] LaddachA GautelM FraternaliF TITINdb-a computational tool to assess titin's role as a disease gene Bioinformatics 2017 33 10.1093/bioinformatics/btx424 586016629077808 Open DOISearch in Google Scholar

17 Cavallo L, Kleinjung J, Fraternali F. POPS: A fast algorithm for solvent accessible surface areas at atomic and residue level. Nucleic Acids Res 2003;31 [DOI: 10.1093/nar/gkg601] CavalloL KleinjungJ FraternaliF POPS: A fast algorithm for solvent accessible surface areas at atomic and residue level Nucleic Acids Res 2003 31 10.1093/nar/gkg601 16900712824328 Open DOISearch in Google Scholar

18 Pires DEV, Ascher DB, Blundell TL. MCSM: Predicting the effects of mutations in proteins using graph-based signatures. Bioinformatics 2014;30 [DOI: 10.1093/bioinformatics/btt691] PiresDEV AscherDB BlundellTL MCSM: Predicting the effects of mutations in proteins using graph-based signatures Bioinformatics 2014 30 10.1093/bioinformatics/btt691 390452324281696 Open DOISearch in Google Scholar

19 den Dunnen JT, Dalgleish R, Maglott DR, Hart RK, Greenblatt MS, Mcgowan-Jordan J, Roux AF, Smith T, Antonarakis SE, Taschner PEM. HGVS Recommendations for the Description of Sequence Variants: 2016 Update. Hum Mutat 2016;37 [DOI: 10.1002/humu.22981] den DunnenJT DalgleishR MaglottDR HartRK GreenblattMS Mcgowan-JordanJ RouxAF SmithT AntonarakisSE TaschnerPEM HGVS Recommendations for the Description of Sequence Variants: 2016 Update Hum Mutat 2016 37 10.1002/humu.22981 26931183 Open DOISearch in Google Scholar

20 Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17 [DOI: 10.1038/gim.2015.30] RichardsS AzizN BaleS BickD DasS Gastier-FosterJ GrodyWW HegdeM LyonE SpectorE VoelkerdingK RehmHL Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology Genet Med 2015 17 10.1038/gim.2015.30 454475325741868 Open DOISearch in Google Scholar

21 Herman DS, Lam L, Taylor MRG, Wang L, Teekakirikul P, Christodoulou D, Conner L, DePalma SR, McDonough B, Sparks E, Teodorescu DL, Cirino AL, Banner NR, Pennell DJ, Graw S, Merlo M, Di Lenarda A, Sinagra G, Bos JM, Ackerman MJ, Mitchell RN, Murry CE, Lakdawala NK, Ho CY, Barton PJR, Cook SA, Mestroni L, Seidman JG, Seidman CE. Truncations of Titin Causing Dilated Cardiomyopathy. N Engl J Med 2012;366 [DOI: 10.1056/nejmoa1110186] HermanDS LamL TaylorMRG WangL TeekakirikulP ChristodoulouD ConnerL DePalmaSR McDonoughB SparksE TeodorescuDL CirinoAL BannerNR PennellDJ GrawS MerloM Di LenardaA SinagraG BosJM AckermanMJ MitchellRN MurryCE LakdawalaNK HoCY BartonPJR CookSA MestroniL SeidmanJG SeidmanCE Truncations of Titin Causing Dilated Cardiomyopathy N Engl J Med 2012 366 10.1056/nejmoa1110186 Open DOISearch in Google Scholar

22 Norton N, Li D, Rampersaud E, Morales A, Martin ER, Zuchner S, Guo S, Gonzalez M, Hedges DJ, Robertson PD, Krumm N, Nickerson DA, Hershberger RE. Exome sequencing and genome-wide linkage analysis in 17 families illustrate the complex contribution of TTN truncating variants to dilated cardiomyopathy. Circ Cardiovasc Genet 2013;6 [DOI: 10.1161/CIRCGENETICS.111.000062] NortonN LiD RampersaudE MoralesA MartinER ZuchnerS GuoS GonzalezM HedgesDJ RobertsonPD KrummN NickersonDA HershbergerRE Exome sequencing and genome-wide linkage analysis in 17 families illustrate the complex contribution of TTN truncating variants to dilated cardiomyopathy Circ Cardiovasc Genet 2013 6 10.1161/CIRCGENETICS.111.000062 381560623418287 Open DOISearch in Google Scholar

23 Tharp CA, Haywood ME, Sbaizero O, Taylor MRG, Mestroni L. The Giant Protein Titin's Role in Cardiomyopathy: Genetic, Transcriptional, and Post-translational Modifications of TTN and Their Contribution to Cardiac Disease. Front. Physiol. 2019;10 [DOI: 10.3389/fphys.2019.01436] TharpCA HaywoodME SbaizeroO TaylorMRG MestroniL The Giant Protein Titin's Role in Cardiomyopathy: Genetic, Transcriptional, and Post-translational Modifications of TTN and Their Contribution to Cardiac Disease Front. Physiol. 2019 10 10.3389/fphys.2019.01436 689275231849696 Open DOISearch in Google Scholar

24 Akhtar MM, Lorenzini M, Cicerchia M, Ochoa JP, Hey TM, Sabater Molina M, Restrepo-Cordoba MA, Dal Ferro M, Stolfo D, Johnson R, Larrañaga-Moreira JM, Robles-Mezcua A, Rodriguez-Palomares JF, Casas G, Peña-Peña ML, Lopes LR, Gallego-Delgado M, Franaszczyk M, Laucey G, Rangel-Sousa D, Basurte M, Palomino-Doza J, Villacorta E, Bilinska Z, Limeres Freire J, Garcia Pinilla JM, Barriales-Villa R, Fatkin D, Sinagra G, Garcia-Pavia P, Gimeno JR, Mogensen J, Monserrat L, Elliott PM. Clinical phenotypes and prognosis of dilated cardiomyopathy caused by truncating variants in the TTN Gene. Circ Hear Fail 2020;[DOI: 10.1161/CIRCHEARTFAILURE.119.006832] AkhtarMM LorenziniM CicerchiaM OchoaJP HeyTM Sabater MolinaM Restrepo-CordobaMA Dal FerroM StolfoD JohnsonR Larrañaga-MoreiraJM Robles-MezcuaA Rodriguez-PalomaresJF CasasG Peña-PeñaML LopesLR Gallego-DelgadoM FranaszczykM LauceyG Rangel-SousaD BasurteM Palomino-DozaJ VillacortaE BilinskaZ Limeres FreireJ Garcia PinillaJM Barriales-VillaR FatkinD SinagraG Garcia-PaviaP GimenoJR MogensenJ MonserratL ElliottPM Clinical phenotypes and prognosis of dilated cardiomyopathy caused by truncating variants in the TTN Gene Circ Hear Fail 2020 10.1161/CIRCHEARTFAILURE.119.006832 32964742 Open DOISearch in Google Scholar

25 Xiao L, Li C, Sun Y, Chen Y, Wei H, Hu D, Yu T, Li X, Jin L, Shi L, Marian AJ, Wang DW. Clinical Significance of Variants in the TTN Gene in a Large Cohort of Patients With Sporadic Dilated Cardiomyopathy. Front Cardiovasc Med 2021;8 [DOI: 10.3389/fcvm.2021.657689] XiaoL LiC SunY ChenY WeiH HuD YuT LiX JinL ShiL MarianAJ WangDW Clinical Significance of Variants in the TTN Gene in a Large Cohort of Patients With Sporadic Dilated Cardiomyopathy Front Cardiovasc Med 2021 8 10.3389/fcvm.2021.657689 812010333996946 Open DOISearch in Google Scholar

26 Zhang C, Zhang H, Wu G, Luo X, Zhang C, Zou Y, Wang H, Hui R, Wang J, Song L. Titin-Truncating Variants Increase the Risk of Cardiovascular Death in Patients With Hypertrophic Cardiomyopathy. Can J Cardiol 2017;33 [DOI: 10.1016/j.cjca.2017.05.020] ZhangC ZhangH WuG LuoX ZhangC ZouY WangH HuiR WangJ SongL Titin-Truncating Variants Increase the Risk of Cardiovascular Death in Patients With Hypertrophic Cardiomyopathy Can J Cardiol 2017 33 10.1016/j.cjca.2017.05.020 28822653 Open DOISearch in Google Scholar

27 Marian AJ. Clinical Interpretation and Management of Genetic Variants. JACC Basic to Transl. Sci. 2020;5 [DOI: 10.1016/j.jacbts.2020.05.013] MarianAJ Clinical Interpretation and Management of Genetic Variants JACC Basic to Transl. Sci. 2020 5 10.1016/j.jacbts.2020.05.013 759193133145465 Open DOISearch in Google Scholar

28 Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR. A method and server for predicting damaging missense mutations. Nat. Methods 2010;7 [DOI: 10.1038/nmeth0410-248] AdzhubeiIA SchmidtS PeshkinL RamenskyVE GerasimovaA BorkP KondrashovAS SunyaevSR A method and server for predicting damaging missense mutations Nat. Methods 2010 7 10.1038/nmeth0410-248 285588920354512 Open DOISearch in Google Scholar

29 Ng PC, Henikoff S. SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Res 2003;31 [DOI: 10.1093/nar/gkg509] NgPC HenikoffS SIFT: Predicting amino acid changes that affect protein function Nucleic Acids Res 2003 31 10.1093/nar/gkg509 16891612824425 Open DOISearch in Google Scholar

30 Schwarz JM, Rödelsperger C, Schuelke M, Seelow D. MutationTaster evaluates disease-causing potential of sequence alterations. Nat. Methods 2010;7 [DOI: 10.1038/nmeth0810-575] SchwarzJM RödelspergerC SchuelkeM SeelowD MutationTaster evaluates disease-causing potential of sequence alterations Nat. Methods 2010 7 10.1038/nmeth0810-575 20676075 Open DOISearch in Google Scholar

31 Kircher M, Witten DM, Jain P, O’roak BJ, Cooper GM, Shendure J. A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet 2014;46 [DOI: 10.1038/ng.2892] KircherM WittenDM JainP O’roakBJ CooperGM ShendureJ A general framework for estimating the relative pathogenicity of human genetic variants Nat Genet 2014 46 10.1038/ng.2892 399297524487276 Open DOISearch in Google Scholar

32 Choi Y, Sims GE, Murphy S, Miller JR, Chan AP. Predicting the Functional Effect of Amino Acid Substitutions and Indels. PLoS One 2012;7 [DOI: 10.1371/journal.pone.0046688] ChoiY SimsGE MurphyS MillerJR ChanAP Predicting the Functional Effect of Amino Acid Substitutions and Indels PLoS One 2012 7 10.1371/journal.pone.0046688 Open DOISearch in Google Scholar

33 Ghosh R, Oak N, Plon SE. Evaluation of in silico algorithms for use with ACMG/AMP clinical variant interpretation guidelines. Genome Biol 2017;18 [DOI: 10.1186/s13059-017-1353-5] GhoshR OakN PlonSE Evaluation of in silico algorithms for use with ACMG/AMP clinical variant interpretation guidelines Genome Biol 2017 18 10.1186/s13059-017-1353-5 Open DOISearch in Google Scholar

34 Lee B, Richards FM. The interpretation of protein structures: Estimation of static accessibility. J Mol Biol 1971;55 [DOI: 10.1016/0022-2836(71)90324-X] LeeB RichardsFM The interpretation of protein structures: Estimation of static accessibility J Mol Biol 1971 55 10.1016/0022-2836(71)90324-X Open DOISearch in Google Scholar

35 Savojardo C, Manfredi M, Martelli PL, Casadio R. Solvent Accessibility of Residues Undergoing Pathogenic Variations in Humans: From Protein Structures to Protein Sequences. Front Mol Biosci 2021;7 [DOI: 10.3389/fmolb.2020.626363]. SavojardoC ManfrediM MartelliPL CasadioR Solvent Accessibility of Residues Undergoing Pathogenic Variations in Humans: From Protein Structures to Protein Sequences Front Mol Biosci 2021 7 10.3389/fmolb.2020.626363 781797033490109 Open DOISearch in Google Scholar