Improved Criteria for the Classification of Titin Variants in Inherited Skeletal Myopathies
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F20%3A00124467" target="_blank" >RIV/00216224:14310/20:00124467 - isvavai.cz</a>
Result on the web
<a href="https://content.iospress.com/articles/journal-of-neuromuscular-diseases/jnd190423" target="_blank" >https://content.iospress.com/articles/journal-of-neuromuscular-diseases/jnd190423</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3233/JND-190423" target="_blank" >10.3233/JND-190423</a>
Alternative languages
Result language
angličtina
Original language name
Improved Criteria for the Classification of Titin Variants in Inherited Skeletal Myopathies
Original language description
BACKGROUND: Extensive genetic screening results in the identification of thousands of rare variants that are difficult to interpret. Because of its sheer size, rare variants in the titin gene (TTN) are detected frequently in any individual. Unambiguous interpretation of molecular findings is almost impossible in many patients with myopathies or cardiomyopathies. OBJECTIVE: To refine the current classification framework for TTN-associated skeletal muscle disorders and standardize the interpretation of TTN variants. METHODS: We used the guidelines issued by the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) to re-analyze TTN genetic findings from our patient cohort. RESULTS: We identified in the classification guidelines three rules that are not applicable to titin-related skeletal muscle disorders; six rules that require disease-/gene-specific adjustments and four rules requiring quantitative thresholds for a proper use. In three cases, the rule strength need to be modified. CONCLUSIONS: We suggest adjustments are made to the guidelines. We provide frequency thresholds to facilitate filtering of candidate causative variants and guidance for the use and interpretation of functional data and co-segregation evidence. We expect that the variant classification framework for TTN-related skeletal muscle disorders will be further improved along with a better understanding of these diseases.
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
30210 - Clinical neurology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Neuromuscular Diseases
ISSN
2214-3599
e-ISSN
2214-3602
Volume of the periodical
7
Issue of the periodical within the volume
2
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
14
Pages from-to
153-166
UT code for WoS article
000685105100008
EID of the result in the Scopus database
2-s2.0-85082147832