The Clinical Genome Resource (ClinGen) Familial Hypercholesterolemia Variant Curation Expert Panel consensus guidelines for LDLR variant classification
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F22%3A00075992" target="_blank" >RIV/65269705:_____/22:00075992 - isvavai.cz</a>
Alternative codes found
RIV/00209775:_____/22:N0000015 RIV/00216224:14110/22:00126147
Result on the web
<a href="https://www.gimjournal.org/article/S1098-3600(21)04140-X/fulltext" target="_blank" >https://www.gimjournal.org/article/S1098-3600(21)04140-X/fulltext</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.gim.2021.09.012" target="_blank" >10.1016/j.gim.2021.09.012</a>
Alternative languages
Result language
angličtina
Original language name
The Clinical Genome Resource (ClinGen) Familial Hypercholesterolemia Variant Curation Expert Panel consensus guidelines for LDLR variant classification
Original language description
Purpose: In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published consensus standardized guidelines for sequence-level variant classification in Mendelian disorders. To increase accuracy and consistency, the Clinical Genome Resource Familial Hypercholesterolemia (FH) Variant Curation Expert Panel was tasked with optimizing the existing ACMG/AMP framework for disease-specific classification in FH. In this study, we provide consensus recommendations for the most common FH-associated gene, LDLR, where >2300 unique FH-associated variants have been identified. Methods: The multidisciplinary FH Variant Curation Expert Panel met in person and through frequent emails and conference calls to develop LDLR-specific modifications of ACMG/AMP guidelines. Through iteration, pilot testing, debate, and commentary, consensus among experts was reached. Results: The consensus LDLR variant modifications to existing ACMG/AMP guidelines include (1) alteration of population frequency thresholds, (2) delineation of loss-of-function variant types, (3) functional study criteria specifications, (4) cosegregation criteria specifications, and (5) specific use and thresholds for in silico prediction tools, among others. Conclusion: Establishment of these guidelines as the new standard in the clinical laboratory setting will result in a more evidence-based, harmonized method for LDLR variant classification worldwide, thereby improving the care of patients with FH.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10603 - Genetics and heredity (medical genetics to be 3)
Result continuities
Project
<a href="/en/project/NU20-02-00261" target="_blank" >NU20-02-00261: Mechanisms of the effect of genetic variants of LDL receptor and the role of genetic variants of lipoprotein(a) in the development of hypercholesterolemia in FH patients</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Genetics in Medicine
ISSN
1098-3600
e-ISSN
1530-0366
Volume of the periodical
24
Issue of the periodical within the volume
2
Country of publishing house
US - UNITED STATES
Number of pages
14
Pages from-to
293-306
UT code for WoS article
000797597400004
EID of the result in the Scopus database
2-s2.0-85123878017