Additional file 6 of Predicting disease severity in metachromatic leukodystrophy using protein activity and a patient phenotype matrix

Additional file 6: Table S5. Enzyme activity of ARSA variants in a genomic construct. Summary of all data used to calculate mean genomic ARSA variant activity. Variants with negative mean percentage of wild-type activity had less sulfatide catabolism than the plate blank. While multiple VUS in gnomAD and the literature are implicated as splice variants, testing all mutants was cost-prohibitive. We triaged variants for testing using the criteria listed in ‘Rationale for testing’. These results provide proof-of-concept for screening in genomic constructs and highlight the technique’s utility in identifying cryptic splice variants. ARSA, arylsulfatase A; BCA, bicinchoninic acid; BLA, beta-lactamase; CDS, coding sequence; gnomAD, Genome Aggregation Database; HGVSc, Human Genome Variation Society coding variant; HGVSp, Human Genome Variation Society protein variant; VUS, variant of unknown significance; WT, wild-type.