Table 1.
Changes in pathogenicity scores of SDHB p.Leu240Pro and p.Leu240Val variants before and after functional validation.
| Variant | ACMG/AMP criteria | Pathogenicity score | |||||
|---|---|---|---|---|---|---|---|
| Population data | Computational data | Functional data | Pre- | Post- | |||
| Leu240Pro | PM2supporting | PP3strong | PS3strong | 5 | VUS | 9 | Likely Pathogenic |
| Leu240Val | PM2supporting | Unclassified | PP3moderate | 1 | VUS | 3 | VUS |
“Pre-” interpretations are made from population (BS1/PM2) and computational prediction (BP4/PP3) data. “Post-” interpretations include our functional data (BS3/PS3). Points per strength level: supporting (±1), moderate (±2), strong (±4), no evidence available (Unclassified, 0). Pathogenicity score thresholds: likely benign (LB), between −6 and −1; VUS, between 0 and 5; likely pathogenic (LP), between 6 and 9; pathogenic (P), greater than 10, respectively.