APOE ε4 variant interpretation and protein numbering discrepancy: a case report.
Burak Dagdelen, Cihat Ozguncu, Ayse Gul Zamani et al.
✦ AI-curated · Sources linked
Case in brief
A 57-year-old man with early-onset Alzheimer's disease underwent next-generation sequencing, revealing a homozygous APOE variant annotated as p.Cys130Arg. This variant corresponds to the APOE ε4-defining rs429358 variant, which is often reported as Cys112Arg in the mature protein sequence. Initially classified as a variant of uncertain significance, further review clarified that both annotations refer to the same allele.
Diagnostic / clinical pearl
Clinicians should be aware that discrepancies in protein numbering can lead to misinterpretation of genetic variants, emphasizing the need for comprehensive genomic analysis.
Why it matters
Understanding the implications of different protein numbering conventions is crucial for accurate genetic counseling and risk assessment in Alzheimer's disease.