Genetics in medicine : official journal of the American College of Medical Genetics · 2026
Multiplatform curation in the development of ACMG/AMP specifications for Von Hippel-Lindau (VHL) disease.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Ritter Deborah I, Badduke Chansonette, Doonanco Kurston, Kang Hio-Chung, Pesaran Tina, Ridd Sarah, Sheen Clare, Farncombe Kirsten M, Giles Rachel H, Luo Minjie, Pipko Neta, Tsoi Chung Ting, McGoldrick Kelly, Mighton Chloe, Abu Kashabeh Razan, Sanabria-Salas Maria C, Talab Yazan, Deka Kamalika B, Jacobs Michelle F, Tuzlali Elif, Gallinger Bailey, Griffith Malachi, Krysiak Kilannin, Machado Jerry, Maher Eamonn R, Tirosh Amit, Kim Raymond H
Аннотация
PURPOSE: The Clinical Genome Resource (ClinGen) Von Hippel-Lindau (VHL) Variant Curation Expert Panel (VCEP) has created variant classification specifications tailored to the VHL gene, including phenotype-driven and evidence-based criteria, utilizing somatic and germline mutational hotspots, along with functional and in silico data.
METHODS: Using the American College of Medical Genetics and Genomics guidance and the ClinGen Sequence Variant Interpretation recommendations, the VCEP made substantial modifications to 8 evidence codes (PVS1, PS3, PS4, PM1, BS2, BS3, BS4, and BP5), whereas 14 had minor changes, and 6 were not used (PM3, PP2, BP1, PP4, PP5/BP6). The VHL VCEP applied 2 literature sets of over >428 articles in Clinical Interpretations of Variants in Cancer and >8700 structured annotations using Hypothesis.
RESULTS: From 31 pilot variants, 15 remained pathogenic/likely pathogenic, and 9 resolved to benign through the stand-alone benign evidence code, whereas 7 variants with initial uncertain classifications lacking additional evidence, remained uncertain.
CONCLUSION: The versioned VHL VCEP Specifications are publicly available in the ClinGen Criteria Specifications Registry and will enhance the transparency and consistency of variant classifications for this highly sequenced hereditary cancer gene.
METHODS: Using the American College of Medical Genetics and Genomics guidance and the ClinGen Sequence Variant Interpretation recommendations, the VCEP made substantial modifications to 8 evidence codes (PVS1, PS3, PS4, PM1, BS2, BS3, BS4, and BP5), whereas 14 had minor changes, and 6 were not used (PM3, PP2, BP1, PP4, PP5/BP6). The VHL VCEP applied 2 literature sets of over >428 articles in Clinical Interpretations of Variants in Cancer and >8700 structured annotations using Hypothesis.
RESULTS: From 31 pilot variants, 15 remained pathogenic/likely pathogenic, and 9 resolved to benign through the stand-alone benign evidence code, whereas 7 variants with initial uncertain classifications lacking additional evidence, remained uncertain.
CONCLUSION: The versioned VHL VCEP Specifications are publicly available in the ClinGen Criteria Specifications Registry and will enhance the transparency and consistency of variant classifications for this highly sequenced hereditary cancer gene.