Table 3.
Observed variants, variant characteristics, and clinical action
| Gene | Variant | Lab interpretation | Allele frequency (gnomAD) | Supporting evidence | FH of pHPT | Clinical action |
|---|---|---|---|---|---|---|
| CASR | ||||||
| c.513C>A; p.Ser171Arg | VUS | Not present | FHH phenotype | + | FHH | |
| c.2332G>C; p.Gly778Arg | VUS | Not present | FHH phenotype | + | FHH | |
| c.505T>C; p.Ser169Pro | VUS | Not present | FHH phenotype | + | FHH | |
| c.206G>A; p.Arg69His | VUS | 7.07 × 10−6 | FHH phenotype | + | FHH | |
| MEN1 | ||||||
| c.1579C>T; p.Arg527X | Pathogenic | Not present | Stopgain | + | MEN1 | |
| c.1618C>T; p.Pro540Ser | Benign (historically pathogenic) | Not present | Reported [12, 13] | – | No action | |
| CDKN1B | ||||||
| c.280C>T; p.Pro94Ser | VUS | 2.84 × 10−5 | + | No action | ||
| RET | ||||||
| c.1597G>A; p.Gly533Ser | VUS | 5.37 × 10−5 | Not MEN2A-related variant | – | Counselled on potential Hirschsprung’s disease | |
| c.718G>C; p.Val240Leu | VUS | 1.26 × 10−5 | Not MEN2A-related variant | – | Counselled on potential Hirschsprung’s disease | |
| CDC73 | ||||||
| c.188T>C; p.Leu63Pro | VUS | Not present | Reported once [6, 16] | + | Counselled on risks and surveillance for CDC73-related disorder | |
| c.238-8G>A, IVS2-8G>A | VUS | not present | Cryptic splice site [14] | – | Counselled on risks and surveillance for CDC73-related disorder | |