EXTERNAL QUALITY ASSESSMENT
In the first trial, out of 286 participants only 16% correctly reported the constitutional FISH result. However, in the second trial, performance improved; with 31% participants out of 422 submitting the correct ISCN. For Neoplasia FISH results, correct reporting of both variants remained low, with only 7% (first trial) and 19% (second trial) of participants submitting the correct ISCN. The most common error across many variants was the inappropriate use of spaces. Notably, for constitutional FISH results, the use of an additional space after the abbreviation ‘nuc ish’ will be compliant according to the latest ISCN 2024 update (ISCN 2024).3 Similar to HGVS nomenclature modules, ISCN modules are also covering basic, intermediate and advanced levels. The initial basic module covering Constitutional karyotyping, was introduced in 2024. In 2025 further modules for basic level covering Neoplasia karyotyping and Constitutional FISH were introduced. In Constitutional karyotyping there
were 575 participants who completed the module. As the modules may be revisited an unlimited number of times, the total recorded submissions was 831. Each time a participant accessed these scenarios, they had to complete different cases. A total of 313 and 154 participants have completed Neoplasia karyotyping and Constitutional FISH, respectively. There have been 859 submissions for Neoplasia karyotyping and 597 submissions for Constitutional FISH. In Constitutional karyotyping, 77% of submissions contained correct nomenclature, with only 23% submitting the incorrect answers. The standard use of ISCN was high overall. The most frequent error was including cell numbers for non-mosaic constitutional results. At least 24 participants incorrectly listed the normal cell line first, instead of last. Another common error was using a semicolon instead of a single slant line to separate cell lines.
For Neoplasia karyotyping, the
standard use of ISCN was high, with 79% of participants providing the correct nomenclature. Among the 21% who submitted incorrect nomenclature,
Germline SNV and CNV classification modules It is challenging to determine if genomic variants detected are linked to the
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Top: Fig 3. Results from CNV classification modules. Above: Fig 4. Results from SNV classification modules.
the most common error was omitting the cell numbers for neoplastic results or in cases for monosomies, especially when the sex chromosome was missing, participants didn’t indicate the monosomy as ‘-X’.
For Constitutional FISH, the standard use of ISCN was not as high as Constitutional karyotyping or Neoplasia karyotyping. Of the 597 submissions, 347 participants (58%) submitted the correct answer, and 250 participants (42%) submitted the incorrect nomenclature.
patient’s clinical presentation, therefore three GENie modules based on germline single nucleotide variants (SNV) and copy number variants (CNV) classification were delivered. These scenarios were completed by 580 and 537 individuals, respectively. To reflect clinical practice, participants had to classify three or six variants based on clinical scenarios. All the cases were generated from a vast bank of variants and included prenatal, postnatal, diagnostic and predictive clinical scenarios. Panels of expert advisors classified the SNVs according to the ACMG3
and ACGS4 guidelines
The growing uptake of the GENie platform indicates a clear demand for continued education, and the outcomes further reveal significant variability in competency levels
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and classified the CNVs according to the ACMG/ClinGen guidelines.5 Overall, participant classification of the CNVs was variable. Figure 3 represents the results of participants who submitted classification for the 22 variants that are available on GENie. The number of participants who submitted the current classification is represented by the dark blue bars, while the number of participants who submitted any other classification is represented by the light blue bars. As the modules are randomised the most common variants
DECEMBER 2025
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Correct classification Other classification
Correct classification Other classification
Number of participants
Number of participants
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