Table 2.
Germline allelic variants identified in probands with (familial) primary hyperaldosteronism/(early onset) hypertension.
| Gene | Nucleotide change1 | Aminoacid change1 | Region | Families | ACMG2,3 | Reference (first report) |
|---|---|---|---|---|---|---|
| (familial) Primary Hyperaldosteronism | ||||||
| CLCN2 | c.65T>A | p.(Met22Lys) | Exon 2 | 1 | VUS-Cool | Scholl et al., 2018 (29) |
| c.71G>A | p.(Gly24Asp) | 1 | VUS-Hot | Fernandes-Rosa et al., 2018 (28) | ||
| c.76T>A | p.(Tyr26Asn) | 1 | VUS-Cool | Scholl et al., 2018 (29) | ||
| c.515G>A | p.(Arg172Gln) | Exon 5 | 8 | P | ||
| c.1084A>T | p.(Lys362*) | Exon 10 | 1 | VUS-Tepid | ||
| c.2593A>C | p.(Ser865Arg) | Exon 24 | 1 | VUS-Cool | ||
| KCNJ5 | c.155G>A | p.(Arg52His) | Exon 2 | 2 | VUS-Tepid | Murthy et al., 2014 (36) |
| c.433G>C | p.(Glu145Gln) | 3 | LP | Monticone et al., 2015 (37) | ||
| c.452G>A | p.(Gly151Glu) | 3 | P | Mulatero et al., 2012 (38) | ||
| c.451G>A | p.(Gly151Arg) | 2 | P | Scholl et al., 2012 (39) | ||
| c.455A>G | p.(Tyr152Cys) | 1 | VUS-Hot | Monticone et al., 2013 (40) | ||
| c.470T>G | p.(Ile157Ser) | 1 | VUS-Warm | Charmandari et al., 2012 (41) | ||
| c.472A>G | p.(Thr158Ala) | 3 | LP | Choi et al., 2011 (23) | ||
| c.736G>A | p.(Glu246Lys) | 1 | VUS-Warm | Murthy et al., 2014 (36) | ||
| c.446_448del | p.(Thr149del) | 1 | VUS-Hot | Pons Fernández et al., 2019 (42) | ||
| CACNA1H | c.587C>T | p.(Ser196Leu) | Exon 5 | 1 | VUS-Tepid | Daniil et al., 2016 (27) |
| c.2669G>A | p.(Arg890His) | Exon 12 | 1 | VUS-Warm | Wulczyn et al., 2019 (43) | |
| c.4645A>G | p.(Met1549Val) | Exon 25 | 5 | LP | Scholl et al., 2015 (26) | |
| c.4647G>C | p.(Met1549Ile) | 1 | VUS-Hot | Daniil et al., 2016 (27) | ||
| c.6248C>T | p.(Pro2083Leu) | Exon 35 | 1 | VUS-Cold | ||
| CACNA1D | c.1208G>A | p.(Gly403Asp) | Exon 8 | 1 | LP | Scholl et al., 2013 (25) |
| c.2310C>G | p.(Ile770Met) | Exon 17 | 1 | LP | ||
| c.776T>A | p.(Val259Asp) | Exon 6 | 1 | VUS-Warm | Semenova et al., 2018 (44) | |
| c.812T>A | p.(Leu271His) | 1 | VUS-Warm | De Mingo Alemany et al., 2020 (45) | ||
| (early onset) Hypertension | ||||||
| KCNJ5 | c.775G>A | p.(Val259Met) | Exon 2 | 1 | VUS-Tepid | Markou et al., 2015 (46) |
| c.834T>A | p.(His278Gln) | 1 | VUS-Tepid | Qin et al., 2019 (47) | ||
| c.1042T>A | p.(Tyr348Asn) | Exon 3 | 1 | VUS-Tepid | Markou et al., 2015 (46) | |
| c.1123C>T | p.(Arg375Trp) | 1 | LB | Qin et al., 2019 (47) | ||
1 RefSeq reference transcript: NM_004366.6 (CLCN2)/NM_000890.5 (KCNJ5)/NM_021098.3 (CACNA1H)/NM_000720.4 (CACNA1D); 2 ACMG/AMP five-tier system: B (Benign), LB (Likely benign), P (Pathogenic), LP (Likely pathogenic), VUS (Variant of uncertain significance); 3 ACGS (Association for Clinical Genomic Science) VUS temperature scale: Ice Cold, Cold, Cool, Tepid, Warm, Hot.