affected individual 6 from family d ( ii - 1 in figure 1 a ) was diag nosed with bradycardia resulting in an arrest and first - degree av block during an episode of fulminant myoc arditis. we therefore cannot exclude a causal role of myoc arditis in this case. however, ( 1 ) the conduction phenotype fits with the phenotypic characteristic of the other five affected individuals we report here; ( 2 ) the affected individual carried bi - allelic truncating variants in popdc2 likely to result in complete lof, which is a known mechanism for disease in animal models; ( 3 ) there was no individual among 125, 748 exomes and 15, 708 genomes in gnomad that carried both variants found in compound heterozygosity ( p. trp188ter and p. leu37serfs 20 ) in the affected individual from family d; ( 4 ) gnomad contains 70 predicted lof popdc2 variants and none of them occurs in the homozygous state; and ( 5 ) knockin mice of the p. trp188ter variant ( found in compound heterozygosity in family d ) displayed stress - induced sinus bradycardia and pauses. in aggregate, these data suggest a causal role for these variants in this individual. while at this stage speculative, some of the genetic cardiomyopathies ( in particular in dsp ) are associated with intermittent myoc ardial inflammatory episodes that appear clinically similar to myoc arditis or sarcoidosis. presentation with ( recurrent ) myoc arditis - like episodes has been reported for arrhythmogenic cardiomyopathy ( acm ). among 560 probands and family members with acm, bariani et al. reported an episode resembling myoc arditis ( i. e., “ hot phase ” ) in 23 cases ( 5 % ), particularly in pediatric affected individuals and carriers of desmoplakin ( mim: 125647 ) variants. furthermore, in a population - based cohort of 336 consecutive affected individuals with acute myoc arditis, a significant enrichment of pathogenic variants in genes associated with dilated or arrhythmogenic cardiomyopathy was found ( 8 % ) in comparison with controls ( < 1 %, p = 0. 0097 ). the question remains whether the myoc arditis exposed the underlying popdc2 - related conduction disease or whether myoc arditis is part of the popdc2 phenotypic spectrum. while we find it unlikely, compound heterozygosity of the truncating popdc2 variants might have been irrelevant in this case, and the phenotype could be fully the consequence of myoc arditis. this study is limited by its relatively small sample size, with four families presenting bi - allelic popdc2 variants, which might have not allowed us to provide the full clinical spectrum of disease associated with recessive popdc2 variants. finally, while population - level data suggest no clinical manifestations in heterozygous carriers, longer - term clinical follow - up would be needed to confirm this in diverse populations and the heterozygous family members in popdc2 families. we here provide robust association of bi - allelic variants in popdc2 with a mendelian autosomal recessive cardiac syndrome consisting of sinus node dysfunction, av conduction defects, and hcm. future studies will help to illuminate the full clinical spectrum of the disease in individuals with bi - allelic variants as well as the clinical presentation of heterozygous carriers, thus elucidating the underlying mechanism of disease. the genetic data from families a – d supporting the current study have not been deposited in a public repository because of ethical restrictions but are available from the corresponding author on request. the pdb coordinates for the popdc2 homology models are available in supplemental information. we thank the families for their participation and collaboration. n. l. is supported by the 10. 13039 / 501100003246 dutch research council ( zonmw veni and off - road ), the auxilium & caritas tulips fellowship, and the de snoo van ' t hoogerhuijs award. c. r. b., a. v. p., and n. l. acknowledge the support from the 10. 13039 / 100002129 dutch heart foundation ( cvon 2018 - 30 predict2 and cvon2014 - 18 concor - genes to c. r. b. ) and the 10. 13039 / 501100003246 netherlands organisation for scientific research ( vici fellowship, 016. 150. 610, to c. r. b. ). this work was supported in part by the 10. 13039 / 100000002 nih awards r35gm128666 ( m. v. a. ) and t32gm092714 ( f. z. b. ), a sloan research fellowship ( m. v. a. ), and an american heart association fellowship 23pre1019634 ( l. w. ). this study makes use of data generated by the decipher community. a full list of centers that contributed to the generation of the data is available from http: / / decipher. sanger. ac. uk and via email from decipher @ sanger. ac. uk. funding for the project was provided by the 10. 13039 / 100010269 wellcome trust. this project has been made possible in part by the chan zuckerberg foundation ( 2019 - 202666 ) to m. noseda and the british heart foundation and deutsches zentrum fur herz - kreislauf - forschung ( bhf / dzhk: sp / 19 / 1 / 34461 ) to m. noseda. mach were supported by the rosetrees trust intermediate project grant ( pgs23 / 100028 ) british heart foundation centre of research excellence ( re / 24 / 130023 ) and nihr imperial biomedical research centre. l. mach was further supported by british heart foundation clinical research training fellowship ( fs / crtf / 23 / 24444 ), british society for heart failure research fellowship, and alexander jansons myoc arditis uk. delphine bichet and florian lesage ( universite de nice sophia antipolis, france ) for sharing the htrek - 1a plasmid. mohamed hosny and magdi yacoub ( magdi yacoub foundation, egypt ) for reviewing the phenotype of affected individuals recruited at their center. r. t. is supported by the canada research chairs program and the philippa and marvin carsley chair in cardiov ascular genetics. the pnc “ hub life science - diagnost ica avanzata ( hls - da ), pnc - e3 - 2022 - 23683266 – cup: c43c22001630001 ” is funded by the italian minister of health. the support of italian ministry of education and research ( mur ) “ dipartimenti di eccellenza program 2023 – 2027 ” - dept of pathophysiology and transplantation, university of milan to d. r. and g. p. c. is gratefully acknowledged. this work was promoted within the european reference network ( ern ) for rare neuromuscular diseases. we thank sara teichmann for sharing data on scrna - seq in human hearts. the graphical abstract was created in https: / / biorender. com. l. monserrat is a shareholder in dilemma solutions sl. d. a. c. is an employee of and may own stock in genedx. h. m. a., v. t., g. s., e. v. i., h. h., d. f. g., a. t. s., and k. s. report employment at decode genetics during the conduct of the study. c. e. reports grants from abbott diagnost ics and novo nordisk outside the submitted work. k. u. k. reports research support from intermountain foundation during the conduct of the study. l. n. reports a stock option grant from culmination bio. h. b. reports lecture fees from amgen, msd, sanofi avensis, bristol myers squibb, and pfizer; grants from novo nordic foundation; and another from novo nordic foundation ( shares ) outside the submitted work. an integrated cell atlas of the lung in health and disease source paper: pmc10287567 single - cell technologies have transformed our understanding of human tissues. yet, studies typically capture only a limited number of donors and disagree on cell type definitions. integrating many single - cell datasets can address these limitations of individual studies and capture the variability present in the population. here we present the integrated human lung cell atlas ( hlca ), combining 49 datasets of the human respiratory system into a single atlas spanning over 2. 4 million cells from 486 individuals. the hlca presents a consensus cell type re - annotation with matching marker genes, including annotations of rare and previously undescribed cell types.