Automated patch-clamp assay reclassifies nine uncertain CACNA1A variants in Australian patients
An automated patch-clamp assay assessed CACNA1A variants in a medRxiv preprint posted October 14, 2026. Researchers expressed 26 benign and 30 pathogenic control variants in Flp-In HEK293 cells with CACNB4 and CACNA2D1. The assay classified all benign controls as functionally normal and 29 of 30 pathogenic controls as abnormal, with 100% specificity and 96.7% sensitivity. In 23 variants from Australian patients, all four variants already classified as pathogenic or likely pathogenic showed abnormal function. Among 19 variants of uncertain significance, 11 were functionally abnormal and nine were reclassified as likely pathogenic after PS3 evidence was integrated with other ACMG/AMP criteria.
The assay could provide functional evidence when clinicians assess CACNA1A variants linked to neurological disorders. The findings come from a preprint that has not been peer reviewed.
Written by the Genomes desk from the primary source cited and linked above and checked against it. Research use only; not medical advice. Corrections: [email protected].