{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T17:42:36Z","timestamp":1793036556148,"version":"4.5.0"},"reference-count":103,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"21","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,11,4]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Primary hypertrophic cardiomyopathy (\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">HCM<\/jats:styled-content>\n                      ) is predominantly a genetic disease causing left ventricular hypertrophy in the absence of other cardiac and systemic metabolic diseases. Currently, limited data exist on the prevalence of clinically actionable gene variants for primary\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">HCM<\/jats:styled-content>\n                      in South Asian Indian (\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">SAI<\/jats:styled-content>\n                      ) patients, which are necessary for minimizing disparities in interpreting ancestry\u2010specific variants. The\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">ClinGen<\/jats:styled-content>\n                      Hereditary Cardiovascular Disorders Gene Curation Expert Panel categorized\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">HCM<\/jats:styled-content>\n                      \u2010causing genes into 5 categories according to their clinical relevance: definitive, strong, moderate, limited, and disputed. However, comprehensive studies examining this classification in\n                      <jats:styled-content style=\"fixed-case\" toggle=\"no\">SAI patients<\/jats:styled-content>\n                      are lacking.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">Whole\u2010exome sequencing was performed for 335 primary SAI patients with HCM, including all known cardiovascular genes and clinically actionable gene categories to determine their allele frequencies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      SAI HCM exomes revealed a total of 193 pathogenic\/likely pathogenic variants and variants of uncertain significance across 26 clinically actionable genes in 119 (35.52%) of 335 cases. The SAI HCM exhibited significantly fewer variants in the 12 definitive category genes compared with other global HCM cohorts (15.77% versus 43.23%;\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;0.0001). For the 5 strong\/moderate genes, no significant difference was observed between the SAI HCM and other global HCM cohorts (3.28% versus 2.73%;\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.3499). Among the 21 limited and disputed genes,\n                      <jats:italic toggle=\"no\">MYH6<\/jats:italic>\n                      showed a significantly higher prevalence of pathogenic\/likely pathogenic variants in the SAI HCM than in the other global HCM cohorts (0.897% versus 0%;\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.0287).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      The clinically actionable gene variants in SAI HCM differed significantly from other global HCM cohorts, specifically\n                      <jats:italic toggle=\"no\">MYBPC3<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"no\">MYH7<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"no\">MYH6<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.042036","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T10:56:46Z","timestamp":1761217006000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Clinically Actionable Hypertrophic Cardiomyopathy Genes in South Asian Indian Patients"],"prefix":"10.1161","volume":"14","author":[{"given":"Vinay J.","family":"Rao","sequence":"first","affiliation":[{"name":"Institute for Stem Cell Science and Regenerative Medicine (BRIC\u2010inStem)","place":["Bengaluru, India"]},{"name":"The University of Trans\u2010Disciplinary Health Sciences and Technology","place":["Bengaluru, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiagarajan","family":"Sairam","sequence":"additional","affiliation":[{"name":"Institute for Stem Cell Science and Regenerative Medicine (BRIC\u2010inStem)","place":["Bengaluru, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andiappan","family":"Rathinavel","sequence":"additional","affiliation":[{"name":"Madurai Medical College and Government Rajaji Hospital","place":["Madurai, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurukkanparampil Sreedharan","family":"Mohanan","sequence":"additional","affiliation":[{"name":"Government Medical College","place":["Kozhikode, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1740-8948","authenticated-orcid":false,"given":"Hisham","family":"Ahamed","sequence":"additional","affiliation":[{"name":"Amrita Institute of Medical Sciences, Amrita Viswa Vidyapeetham (Amrita University)","place":["Kochi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4509-7515","authenticated-orcid":false,"given":"Jayaprakash","family":"Shenthar","sequence":"additional","affiliation":[{"name":"Sri Jayadeva Institute of Cardiovascular Sciences and Research","place":["Bengaluru, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7831-9570","authenticated-orcid":false,"given":"Perundurai S.","family":"Dhandapany","sequence":"additional","affiliation":[{"name":"Institute for Stem Cell Science and Regenerative Medicine (BRIC\u2010inStem)","place":["Bengaluru, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90274-I"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1295-434"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90054-x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.92.4.785"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.01.019"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2021.12.002"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1710575"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehad372"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa075463"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.105.593558"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu284"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-021-00608-2"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2024.12.010"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2012.02.068"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2014-306387"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.123.033565"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001250"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehad194"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ihj.2025.03.013"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.205"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-00764-0"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab424"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.10.001"},{"key":"e_1_3_2_25_2","first-page":"424","article-title":"Genetic studies of hypertrophic cardiomyopathy in Singaporeans identify variants in TNNI3 and TNNT2 that are common in Chinese patients","volume":"13","author":"Pua CJ","year":"2020","unstructured":"Pua CJ, Tham N, Chin CWL, Walsh R, Khor CC, Toepfer CN, Repetti GG, Garfinkel AC, Ewoldt JK, Cloonan P, et\u00a0al. Genetic studies of hypertrophic cardiomyopathy in Singaporeans identify variants in TNNI3 and TNNT2 that are common in Chinese patients. Circulation. 2020;13:424\u2013434.","journal-title":"Circulation"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep16609"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2019.4638"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.120.019978"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.119.002460"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2008.02.082"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abb3991"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYP.0000000000000066"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.09.583"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2013.07.001"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2019.03.059"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3495"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2024.1384408"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2016.00397"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(10)80189-5"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.08.074"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2021-107866"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.258"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.01.004"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1153"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.90"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1793-z"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa923"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0375-z"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2015.10.001"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.112.270207"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2020-316913"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells12020337"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2021.08.022"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00586-4"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw603"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2007.06.009"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.08.058"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2005.10.008"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2005.08.006"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2012-101231"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.04.151"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1161\/hc0402.102990"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2021.07.014"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-13-69"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1161\/circgenetics.116.001685"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2024.132273"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-017-3123-9"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mgene.2019.100567"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0039-1694829"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13353-024-00855-2"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.119.002500"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.249"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jccase.2021.09.011"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2024.103533"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-67201-8"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.894635"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00838"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0050053"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2009.09.019"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17081239"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8040463"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jelectrocard.2019.01.002"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.507699"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2015.11.048"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2012-101270"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.1002\/uog.19042"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00091.2016"},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-018-1806-y"},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005963"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37108"},{"key":"e_1_3_2_92_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq315"},{"key":"e_1_3_2_93_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3970"},{"key":"e_1_3_2_94_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2014.09.048"},{"key":"e_1_3_2_95_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.109.912345"},{"key":"e_1_3_2_96_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ppedcard.2010.11.008"},{"key":"e_1_3_2_97_2","doi-asserted-by":"publisher","DOI":"10.1111\/anec.12840"},{"key":"e_1_3_2_98_2","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12116"},{"key":"e_1_3_2_99_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2015.2361"},{"key":"e_1_3_2_100_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-011-1077-x"},{"key":"e_1_3_2_101_2","doi-asserted-by":"publisher","DOI":"10.1089\/dna.2014.2650"},{"key":"e_1_3_2_102_2","doi-asserted-by":"publisher","DOI":"10.1089\/dna.2011.1366"},{"key":"e_1_3_2_103_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.065987"},{"key":"e_1_3_2_104_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08365"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.125.042036","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T11:22:04Z","timestamp":1780485724000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.125.042036"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,4]]},"references-count":103,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2025,11,4]]}},"alternative-id":["10.1161\/JAHA.125.042036"],"URL":"https:\/\/doi.org\/10.1161\/jaha.125.042036","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,4]]},"assertion":[{"value":"2025-02-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e042036"}}