Genetic screening evaluation examines translation-extending stop-loss and frameshift variants in carrier screening cohorts, highlighting key challenges in variant classification.
Stop-loss and frameshift variants extending translation beyond the reference stop codon into the 3’ untranslated region are predicted to generate extended proteins. Frameshift variants extending the sequence also disrupt the original amino acid sequence, which may impact functionally relevant regions. The prevalence, mechanism of pathogenicity, and clinical impact of these variants are not well characterized, which presents a challenge for variant interpretation/classification; hence, we sought to evaluate these types of variants within our internal dataset.
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Flores et al. (2024) studied this question.
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