{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T19:17:55Z","timestamp":1787944675147,"version":"build-2784847793"},"reference-count":65,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Research, Innovation, and Digitalization","award":["PN-IV-P8-8.3-ROMD-2023-0259"],"award-info":[{"award-number":["PN-IV-P8-8.3-ROMD-2023-0259"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: KDIGO supports molecular testing in selected autosomal dominant polycystic kidney disease (ADPKD) scenarios and targeted next-generation sequencing panels when broader evaluation is warranted; however, gene inclusion alone establishes neither analytical completeness nor clinical reportability. Methods: We designed and evaluated a 28-gene ADPKD-spectrum hybrid-capture panel in a 16-sample, two-configuration pilot using 694 analytical target intervals per sample. Multiplex ligation-dependent probe amplification assessed dosage in suspected PKD1-related disease or TSC2\/PKD1 contiguous-gene deletion, and whole-exome sequencing selectively supported short-read reidentification. Results: In the primary eight-sample dataset, 4592\/5552 observations (82.7%) had interval mean depth \u226520\u00d7, 4256\/5552 (76.7%) had interval minimum depth \u226520\u00d7, and 89.6% of interval-record bases reached \u226510\u00d7. Nine genes (FLCN, GANAB, HNF1B, PRKCSH, REN, SEC61A1, TSC2, UMOD and VHL) met mean depth \u226520\u00d7 throughout; six also met the minimum-depth criterion. For PKD1, 45\/46 intervals met both criteria in all samples, but exon 1 remained undercovered, and nominal depth in duplicated sequence did not establish authentic-locus callability. Signals were observed at all four positive-comparator loci, although two lacked sufficient support for independent reporting. Seven of nine panel-first cases yielded observations: one HNF1B and one unique-locus PKD1 finding were supported, whereas four duplicated-sequence PKD1 findings remained confirmation-dependent. Conclusions: Responsible implementation requires explicit analytical boundaries and staged complementary testing.<\/jats:p>","DOI":"10.3390\/diagnostics16172770","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T18:33:52Z","timestamp":1787942032000},"page":"2770","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Guidelines to Practice: Pilot Implementation and Analytical Boundaries of a Focused ADPKD-Spectrum Gene Panel"],"prefix":"10.3390","volume":"16","author":[{"given":"Ramona G.","family":"Babici","sequence":"first","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"},{"name":"Dialysis and Renal Transplant Center, Nephrology Clinic, Dr. C.I. Parhon University Hospital, 700503 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5372-9901","authenticated-orcid":false,"given":"Iuliu C.","family":"Ivanov","sequence":"additional","affiliation":[{"name":"Molecular Diagnosis Department, Regional Institute of Oncology, 700483 Iasi, Romania"},{"name":"Faculty of Biology, Alexandru Ioan Cuza University of Iasi, 700506 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogdan D.","family":"Agavriloaei","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"},{"name":"Dialysis and Renal Transplant Center, Nephrology Clinic, Dr. C.I. Parhon University Hospital, 700503 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Irina L.","family":"Mititiuc","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"},{"name":"Dialysis and Renal Transplant Center, Nephrology Clinic, Dr. C.I. Parhon University Hospital, 700503 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5551-6077","authenticated-orcid":false,"given":"Gianina","family":"Dodi","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Mihaiela L.","family":"Drago\u0219","sequence":"additional","affiliation":[{"name":"Molecular Diagnosis Department, Regional Institute of Oncology, 700483 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0900-0096","authenticated-orcid":false,"given":"Stela","family":"Racovi\u021b\u0103","sequence":"additional","affiliation":[{"name":"Nicolae Testemi\u021banu State University of Medicine and Pharmacy, MD-2005 Chisinau, Moldova"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2030-1436","authenticated-orcid":false,"given":"Alexandra","family":"Savuca","sequence":"additional","affiliation":[{"name":"Origyn Fertility Center, 700032 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Mugurel","family":"Apetrii","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"},{"name":"Dialysis and Renal Transplant Center, Nephrology Clinic, Dr. C.I. Parhon University Hospital, 700503 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2183-0690","authenticated-orcid":false,"given":"Roxana","family":"Popescu","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"},{"name":"Medical Genetics Department, Saint Mary Emergency Children\u2019s Hospital, 700309 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9985-2486","authenticated-orcid":false,"given":"Adrian C.","family":"Covic","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"},{"name":"Dialysis and Renal Transplant Center, Nephrology Clinic, Dr. C.I. Parhon University Hospital, 700503 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0901-759X","authenticated-orcid":false,"given":"Cristina","family":"Rusu","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"},{"name":"Medical Genetics Department, Saint Mary Emergency Children\u2019s Hospital, 700309 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"(2025). Kidney Disease: Improving Global Outcomes (KDIGO) ADPKD Work Group. KDIGO 2025 Clinical Practice Guideline for the Evaluation, Management, and Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD). Kidney Int., 107, S1\u2013S239.","DOI":"10.1016\/j.kint.2024.07.009"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1681\/ASN.2019030298","article-title":"ALG9 Mutation Carriers Develop Kidney and Liver Cysts","volume":"30","author":"Besse","year":"2019","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.kint.2020.02.022","article-title":"Clinical Spectrum, Prognosis and Estimated Prevalence of DNAJB11-Kidney Disease","volume":"98","author":"Huynh","year":"2020","journal-title":"Kidney Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1016\/j.ajhg.2022.06.013","article-title":"Monoallelic Pathogenic ALG5 Variants Cause Atypical Polycystic Kidney Disease and Interstitial Fibrosis","volume":"109","author":"Lemoine","year":"2022","journal-title":"Am. J. Hum. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1016\/j.ajhg.2016.05.004","article-title":"Mutations in GANAB, Encoding the Glucosidase II\u03b1 Subunit, Cause Autosomal-Dominant Polycystic Kidney and Liver Disease","volume":"98","author":"Porath","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1007\/s00467-015-3142-2","article-title":"HNF1B-Associated Clinical Phenotypes: The Kidney and Beyond","volume":"31","author":"Bockenhauer","year":"2016","journal-title":"Pediatr. Nephrol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1038\/ki.2008.485","article-title":"Characterization of Large Rearrangements in Autosomal Dominant Polycystic Kidney Disease and the PKD1\/TSC2 Contiguous Gene Syndrome","volume":"74","author":"Consugar","year":"2008","journal-title":"Kidney Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.pediatrneurol.2021.07.011","article-title":"Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations","volume":"123","author":"Northrup","year":"2021","journal-title":"Pediatr. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"143","DOI":"10.2215\/CJN.04230321","article-title":"Guidelines for Genetic Testing and Management of Alport Syndrome","volume":"17","author":"Savige","year":"2022","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1038\/s41431-024-01671-2","article-title":"ERN GENTURIS Clinical Practice Guidelines for the Diagnosis, Surveillance and Management of People with Birt-Hogg-Dub\u00e9 Syndrome","volume":"32","author":"Geilswijk","year":"2024","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/ejhg.2010.175","article-title":"Von Hippel\u2013Lindau Disease: A Clinical and Scientific Review","volume":"19","author":"Maher","year":"2011","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"101","DOI":"10.2215\/CJN.0000000000000564","article-title":"Utility of Genetic Testing in Adults with CKD: A Systematic Review and Meta-Analysis","volume":"20","author":"Schott","year":"2025","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Mantovani, V., Bin, S., Graziano, C., Capelli, I., Minardi, R., Aiello, V., Ambrosini, E., Cristalli, C.P., Mattiaccio, A., and Pariali, M. (2020). Gene Panel Analysis in a Large Cohort of Patients With Autosomal Dominant Polycystic Kidney Disease Allows the Identification of 80 Potentially Causative Novel Variants and the Characterization of a Complex Genetic Architecture in a Subset of Families. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.00464"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1038\/s41436-020-0816-3","article-title":"Matching Clinical and Genetic Diagnoses in Autosomal Dominant Polycystic Kidney Disease Reveals Novel Phenocopies and Potential Candidate Genes","volume":"22","author":"Baatz","year":"2020","journal-title":"Genet. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"101186","DOI":"10.1016\/j.xkme.2025.101186","article-title":"Results of Multigene Panel Testing, Including PKD1, in >1200 Patients With Cystic Kidney Disease: A Retrospective Analysis","volume":"8","author":"Tapper","year":"2026","journal-title":"Kidney Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41525-025-00477-5","article-title":"Targeted Long-Read Sequencing Enables Higher Diagnostic Yield of ADPKD by Accurate PKD1 Genetic Analysis","volume":"10","author":"Sun","year":"2025","journal-title":"npj Genom. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/s41436-019-0666-z","article-title":"Diagnostic Gene Sequencing Panels: From Design to Report\u2014A Technical Standard of the American College of Medical Genetics and Genomics (ACMG)","volume":"22","author":"Bean","year":"2020","journal-title":"Genet. Med."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Eisenberger, T., Decker, C., Hiersche, M., Hamann, R.C., Decker, E., Neuber, S., Frank, V., Bolz, H.J., Fehrenbach, H., and Pape, L. (2015). An Efficient and Comprehensive Strategy for Genetic Diagnostics of Polycystic Kidney Disease. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0116680"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1038\/s41436-021-01139-4","article-title":"Next-Generation Sequencing for Constitutional Variants in the Clinical Laboratory, 2021 Revision: A Technical Standard of the American College of Medical Genetics and Genomics (ACMG)","volume":"23","author":"Rehder","year":"2021","journal-title":"Genet. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4141","DOI":"10.1038\/s41598-019-40761-w","article-title":"PKD1 Duplicated Regions Limit Clinical Utility of Whole Exome Sequencing for Genetic Diagnosis of Autosomal Dominant Polycystic Kidney Disease","volume":"9","author":"Ali","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"100316","DOI":"10.1016\/j.gim.2022.09.017","article-title":"Points to Consider in the Detection of Germline Structural Variants Using Next-Generation Sequencing: A Statement of the American College of Medical Genetics and Genomics (ACMG)","volume":"25","author":"Raca","year":"2023","journal-title":"Genet. Med."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Butnariu, L.I., Russu, R., Babici, R.G., B\u0103giag, A., Trandafir, L.M., \u021aarc\u0103, E., Popovici, P., Gimiga, N., and Starcea, I.M. (2026). The Importance of Molecular Testing in the Diagnosis of Genetic Syndromes with Chronic Kidney Disease: Genotype\u2013Phenotype Correlations. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27052362"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3094","DOI":"10.1093\/bioinformatics\/bty191","article-title":"Minimap2: Pairwise Alignment for Nucleotide Sequences","volume":"34","author":"Li","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1093\/bioinformatics\/btw753","article-title":"Edlib: A C\/C++ Library for Fast, Exact Sequence Alignment Using Edit Distance","volume":"33","year":"2017","journal-title":"Bioinformatics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1038\/ejhg.2016.48","article-title":"Whole-Genome Sequencing Overcomes Pseudogene Homology to Diagnose Autosomal Dominant Polycystic Kidney Disease","volume":"24","author":"Mallawaarachchi","year":"2016","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.jmoldx.2012.02.007","article-title":"A Novel Long-Range PCR Sequencing Method for Genetic Analysis of the Entire PKD1 Gene","volume":"14","author":"Tan","year":"2012","journal-title":"J. Mol. Diagn."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1093\/clinchem\/hvae030","article-title":"Comprehensive Analysis of PKD1 and PKD2 by Long-Read Sequencing in Autosomal Dominant Polycystic Kidney Disease","volume":"70","author":"Xu","year":"2024","journal-title":"Clin. Chem."},{"key":"ref_28","unstructured":"Association for Clinical Genomic Science (2026, August 10). ACGS Best Practice Guidelines for Variant Classification in Rare Disease 2024, Version 1.2. Available online: https:\/\/www.acgs.uk.com\/quality\/best-practice-guidelines\/."},{"key":"ref_29","unstructured":"ClinGen Sequence Variant Interpretation Working Group (2026, August 10). Recommendation for Absence\/Rarity Criterion PM2, Version 1.0. Clinical Genome Resource. Available online: https:\/\/www.clinicalgenome.org\/docs\/pm2-recommendation-for-absence-rarity\/."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1002\/humu.23626","article-title":"Recommendations for Interpreting the Loss of Function PVS1 ACMG\/AMP Variant Criterion","volume":"39","author":"Pesaran","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.ajhg.2023.11.009","article-title":"ClinGen Guidance for Use of the PP1\/BS4 Co-Segregation and PP4 Phenotype Specificity Criteria for Sequence Variant Pathogenicity Classification","volume":"111","author":"Biesecker","year":"2024","journal-title":"Am. J. Hum. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1038\/gim.2018.42","article-title":"The ACMG\/AMP Reputable Source Criteria for the Interpretation of Sequence Variants","volume":"20","author":"Biesecker","year":"2018","journal-title":"Genet. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s13073-019-0690-2","article-title":"Recommendations for Application of the Functional Evidence PS3\/BS3 Criterion Using the ACMG\/AMP Sequence Variant Interpretation Framework","volume":"12","author":"Brnich","year":"2020","journal-title":"Genome Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1016\/j.ajhg.2022.10.013","article-title":"Calibration of Computational Tools for Missense Variant Pathogenicity Classification and ClinGen Recommendations for PP3\/BP4 Criteria","volume":"109","author":"Pejaver","year":"2022","journal-title":"Am. J. Hum. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"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","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1002\/humu.24088","article-title":"Fitting a Naturally Scaled Point System to the ACMG\/AMP Variant Classification Guidelines","volume":"41","author":"Tavtigian","year":"2020","journal-title":"Hum. Mutat."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1002\/humu.22103","article-title":"Autosomal Dominant Polycystic Kidney Disease: Comprehensive Mutation Analysis of PKD1 and PKD2 in 700 Unrelated Patients","volume":"33","author":"Chen","year":"2012","journal-title":"Hum. Mutat."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"30850","DOI":"10.1038\/srep30850","article-title":"Deciphering Variability of PKD1 and PKD2 in an Italian Cohort of 643 Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD)","volume":"6","author":"Carrera","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1681\/ASN.2012070650","article-title":"Type of PKD1 Mutation Influences Renal Outcome in ADPKD","volume":"24","author":"Chen","year":"2013","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1093\/ndt\/gfq720","article-title":"Novel PKD1 and PKD2 Mutations in Autosomal Dominant Polycystic Kidney Disease (ADPKD)","volume":"26","author":"Hoefele","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_41","unstructured":"National Center for Biotechnology Information (2026, August 19). ClinVar Variation ID 374097: NM_001009944.3(PKD1):c.8311G>A (p.Glu2771Lys), Available online: https:\/\/www.ncbi.nlm.nih.gov\/clinvar\/variation\/374097\/."},{"key":"ref_42","unstructured":"National Center for Biotechnology Information (2026, August 18). ClinVar Variation ID 562302: NM_001009944.3(PKD1):c.2180T>C (p.Leu727Pro), Available online: https:\/\/www.ncbi.nlm.nih.gov\/clinvar\/variation\/562302\/."},{"key":"ref_43","unstructured":"Clinical Genome Resource (2026, August 20). ClinGen Allele Registry CA16043003: NM_001009944.3(PKD1):c.8369del (p.Pro2790fs). Available online: https:\/\/reg.clinicalgenome.org\/redmine\/projects\/registry\/genboree_registry\/by_caid?caid=CA16043003."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1681\/ASN.2011101032","article-title":"Identification of Gene Mutations in Autosomal Dominant Polycystic Kidney Disease through Targeted Resequencing","volume":"23","author":"Rossetti","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1681\/ASN.2006121387","article-title":"Comprehensive Molecular Diagnostics in Autosomal Dominant Polycystic Kidney Disease","volume":"18","author":"Rossetti","year":"2007","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.jmoldx.2013.10.005","article-title":"Molecular Diagnosis of Autosomal Dominant Polycystic Kidney Disease Using Next-Generation Sequencing","volume":"16","author":"Tan","year":"2014","journal-title":"J. Mol. Diagn."},{"key":"ref_47","unstructured":"(2026, August 17). Genome Aggregation Database. gnomAD v4.1.0. Available online: https:\/\/gnomad.broadinstitute.org\/."},{"key":"ref_48","first-page":"86","article-title":"Screening the 3\u2019 Region of the Polycystic Kidney Disease 1 (PKD1) Gene Reveals Six Novel Mutations","volume":"58","author":"Peral","year":"1996","journal-title":"Am. J. Hum. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"He, W.-B., Xiao, W.-J., Tan, Y.-Q., Zhao, X.-M., Li, W., Zhang, Q.-J., Zhong, C.-G., Li, X.-R., Hu, L., and Lu, G.-X. (2018). Novel Mutations of PKD Genes in Chinese Patients Suffering from Autosomal Dominant Polycystic Kidney Disease and Seeking Assisted Reproduction. BMC Med. Genet., 19.","DOI":"10.1186\/s12881-018-0693-7"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1161\/CIRCULATIONAHA.118.034731","article-title":"Polycystin-1 Assembles With Kv Channels to Govern Cardiomyocyte Repolarization and Contractility","volume":"140","author":"Altamirano","year":"2019","journal-title":"Circulation"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s41231-023-00157-5","article-title":"Exploring the clinical and genetical spectrum of ADPKD in Chile to assess ProPKD score as a risk prediction tool","volume":"8","author":"Bayyad","year":"2023","journal-title":"Transl. Med. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1046\/j.1523-1755.2002.00326.x","article-title":"A Complete Mutation Screen of the ADPKD Genes by DHPLC","volume":"61","author":"Rossetti","year":"2002","journal-title":"Kidney Int."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Obeidova, L., Elisakova, V., Stekrova, J., Reiterova, J., Merta, M., Tesar, V., Losan, F., and Kohoutova, M. (2014). Novel Mutations of PKD Genes in the Czech Population with Autosomal Dominant Polycystic Kidney Disease. BMC Med. Genet., 15.","DOI":"10.1186\/1471-2350-15-41"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Vouk, K., Strmecki, L., Stekrova, J., Reiterova, J., Bidovec, M., Hudler, P., Kenig, A., Jereb, S., Zupanic-Pajnic, I., and Balazic, J. (2006). PKD1 and PKD2 Mutations in Slovenian Families with Autosomal Dominant Polycystic Kidney Disease. BMC Med. Genet., 7.","DOI":"10.1186\/1471-2350-7-6"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"16981","DOI":"10.1073\/pnas.252484899","article-title":"Cleavage of Polycystin-1 Requires the Receptor for Egg Jelly Domain and Is Disrupted by Human Autosomal-Dominant Polycystic Kidney Disease 1-Associated Mutations","volume":"99","author":"Qian","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.jmoldx.2023.03.012","article-title":"Recommendations for Next-Generation Sequencing Germline Variant Confirmation: A Joint Report of the Association for Molecular Pathology and National Society of Genetic Counselors","volume":"25","author":"Crooks","year":"2023","journal-title":"J. Mol. Diagn."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/s41436-019-0686-8","article-title":"Technical Standards for the Interpretation and Reporting of Constitutional Copy-Number Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen)","volume":"22","author":"Riggs","year":"2020","journal-title":"Genet. Med."},{"key":"ref_58","first-page":"932","article-title":"Analysis of PDK1 Gene Variants and Prenatal Diagnosis for Eight Pedigrees Affected with Autosomal Dominant Polycystic Kidney Disease","volume":"39","author":"Li","year":"2022","journal-title":"Zhonghua Yi Xue Yi Chuan Xue Za Zhi"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Agavriloaei, B.D., Costache, R.C., Babici, R.G., Racovi\u021b\u0103, S., Dodi, G., Covic, A.C., and Mititiuc, I.L. (2025). The Prospect of Novel Orphan Therapeutic Protocol for TSC2\/PKD1 Contiguous Gene Syndrome: A Case Report. BMC Nephrol., 26.","DOI":"10.1186\/s12882-025-04088-1"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Kinoshita, M., Higashihara, E., Kawano, H., Higashiyama, R., Koga, D., Fukui, T., Gondo, N., Oka, T., Kawahara, K., and Rigo, K. (2016). Technical Evaluation: Identification of Pathogenic Mutations in PKD1 and PKD2 in Patients with Autosomal Dominant Polycystic Kidney Disease by Next-Generation Sequencing and Use of a Comprehensive New Classification System. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0166288"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/ng.2543","article-title":"Mutations Causing Medullary Cystic Kidney Disease Type 1 Lie in a Large VNTR in MUC1 Missed by Massively Parallel Sequencing","volume":"45","author":"Kirby","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.jmoldx.2017.11.003","article-title":"Standards and Guidelines for Validating Next-Generation Sequencing Bioinformatics Pipelines: A Joint Recommendation of the Association for Molecular Pathology and the College of American Pathologists","volume":"20","author":"Roy","year":"2018","journal-title":"J. Mol. Diagn."},{"key":"ref_63","unstructured":"(2022). SureSelect XT HS2 DNA with Post-Capture Pooling: Quick Start Protocol (Standard No. G9983-90500 Rev A0)."},{"key":"ref_64","unstructured":"(2022). SureSelect XT HS2 DNA with Pre-Capture Pooling: Quick Start Protocol (Standard No. G9985-90500 Rev A0)."},{"key":"ref_65","unstructured":"(2022). SureSelect Enzymatic Fragmentation Kit Protocol (Standard No. G9702-90050)."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/17\/2770\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T18:44:25Z","timestamp":1787942665000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/17\/2770"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,28]]},"references-count":65,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["diagnostics16172770"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics16172770","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,28]]}}}