Table 2 Twelve novel and ten previously reported PPA2 variants associated with sudden unexplained death in infancy or sudden cardiac death.
From: PPA2-associated sudden cardiac death: extending the clinical and allelic spectrum in 20 new families
Variant | Exome count | Genome count | Total freq. | dbSNP | Genomic coordinates | ACMG/AMP classification [6] | Family |
|---|---|---|---|---|---|---|---|
This study | |||||||
c.250C>T;p.(Arg84*) | 2 (245032) | 0 | 0.00001 | rs781655422 | Chr4(GRCh38):g.105453615G>A | Pathogenic: PVS1-VSTR; PM2-MOD | 15 |
c.340A>G;p.(Met114Val) | 4 (240494) | 1 (31404) | 0.00002 | rs375129675 | Chr4(GRCh38):g.105446484T>C | Likely pathogenic: PS3-MOD; PM2-MOD; PM3-MOD | 1, 2, 3a |
c.346C>T;p.(Pro116Ser) | 11 (239402) | 0 | 0.00005 | rs373735128 | Chr4(GRCh38):g.105446478G>A | Likely pathogenic: PS3-MOD; PM2-MOD; PM3-MOD; PP3-SUP | 8 |
c.389C>T;p.(Ala130Val) | 0 | 0 | 0 | na | Chr4(GRCh38):g.105446435G>A | Likely pathogenic: PS3-MOD; PM2-MOD; PM3-MOD; PP3-SUP | 15 |
c.443C>G;p.(Thr148Ser) | 1 (243948) | 1 (31340) | 0.00005 | rs778534602 | Chr4(GRCh38):g.105438035G>C | Likely pathogenic: PS3-MOD; PM2-MOD; PM3-MOD; PP3-SUP | 12 |
c.476C>T;p.(Thr159Met) | 12 (243948) | 0 | 0.00005 | rs752062224 | Chr4(GRCh38):g.105438002G>A | Likely pathogenic: PS3-MOD; PM2-MOD; PM3-STR; PP3-SUP | 7, 13, 18 |
c.503T>C;p.(Ile168Thr) | 6 (246480) | 0 | 0.00002 | rs760824971 | Chr4(GRCh38):g.105437975A>G | Likely pathogenic: PS3-STR; PM2-MOD; PM3-SUP; PP3-SUP | 14a |
c.606G>C;p.(Trp202Cys) | 1 (248128) | 0 | 0.00001 | na | Chr4(GRCh38)g.105424245C>G | Likely pathogenic: PS3-MOD; PM2-MOD; PM3-MOD; PP3-SUP | 11 |
c.655+5G>A (splice site) | 1 (237254) | 0 | 0.00001 | rs1409680543 | Chr4(GRCh38):g.105424191C>T | VUS: PM2-MOD; PP3-SUP | 2 |
c.686G>T;p.(Gly229Val) | 0 | 0 | 0 | na | Chr4(GRCh38):g.105399134C>A | Likely pathogenic: PS3-MOD; PM2-MOD; PP3-SUP | 20a |
c.833T>C;p.(Leu278Ser) | 0 | 0 | 0 | na | Chr4(GRCh38):g.105396285A>G | Likely pathogenic: PS3-MOD; PM2-MOD; PM3-MOD; PP3-SUP | 17 |
c.938C>A;p.(Ser313*) | 9 (250934) | 1 (31382) | 0.00004 | rs151331559 | Chr4(GRCh38):g.105386568G>T | Pathogenic: PVS1-VSTR; PM2-MOD | 10, 12 |
c.182C>T;p.(Ser61Phe) | 2 (247094) | 0 | 0.00001 | rs772083375 | Chr4(GRCh38):g.105456721G>A | Likely pathogenic: PS3-SUP; PM2-MOD; PP1-MOD; PP3-SUP | |
c.280A>G;p.(Met94Val) | 0 | 0 | 0 | rs1057517679 | Chr4(GRCh38):g.105449391T>C | Likely pathogenic: PS3-SUP; PM2-MOD; PM3-MOD; PP3-SUP | |
c.318G>T;p.(Met106Ile) | 0 | 0 | 0 | rs1057517680 | Chr4(GRCh38):g.105449353C>A | VUS PM2-MOD; PM3-MOD; PP3-SUP | |
c.380G>T;p.(Arg127Leu) | 37 (244404) | 7 (31390) | 0.00016 | rs139076647 | Chr4(GRCh38):g.105446444C>A | Pathogenic: PS3-SUP; PM2-MOD; PM3-STR; PP1-STR; PP3-SUP | 6, 9a, 16 |
c.442A>T;p.(Thr148Ser) | 0 | 0 | 0 | na | Chr4(GRCh38):g.105438036A>T | Likely pathogenic: PS1-STR; PM2-MOD; PM3-MOD; PP3-SUP | |
c.500C>T;p.(Pro167Leu) | 4 (245870) | 4 (245870) | 0.00002 | rs546693824 | Chr4(GRCh38):g.105437978G>A | Likely pathogenic: PS3-SUP; PM2-MOD; PM3-SUP; PP1-STR; PP3-SUP | 19a |
c.514G>A;p.(Glu172Lys) | 120 (243704) | 27 (31376) | 0.00053 | rs146013446 | Chr4(GRCh38):g.105437964C>T | Pathogenic: PS3-STR; PM2-MOD; PP1-STR; PP3-SUP | 1,4,5,6,7,10,1113,16,17,18 |
c.556G>A;p.(Val186Met) | 0 | 0 | 0 | na | Chr4(GRCh38):g.105424295C>T | Likely pathogenic: PS3-SUP; PM2-MOD; PM3-MOD; PP3-SUP | |
c.683C>T;p.(Pro228Leu) | 49 (242474) | 9 (31366) | 0.00021 | rs138215926 | Chr4(GRCh38):g.105399137G>A | Pathogenic: PS3-SUP, PM2-MOD, PM3-MOD, PP1-STR, PP3-SUP | 4, 5, 8 |
c.881A>C;p.(Gln294Pro) | 0 | 0 | 0 | rs1057517678 | Chr4(GRCh38):g.105386625T>G | Likely pathogenic: PS3-SUP; PM2-MOD; PM3-MOD; PP1-MOD; BP4-SUP | |
