Table 1.
Variants detected in the NBS program for Pompe disease
| Variant No | rs IDs | Nucleic acid | Amino acid | Location | Classification | |||
|---|---|---|---|---|---|---|---|---|
| Pompe disease GAA variant database | ClinVar Miner | PolyPhen-2 (score) | ||||||
| Disease-associated variants | 2 | rs772534106 | c.317G > A | p.R106H | Exon 2 | Potentially less severe | Uncertain significance | Probably damaging (1.000) |
| 4 | – | c.439G > A | p.G147S | Exon 2 | NR | NR | Probably damaging (0.989) | |
| 5 | rs376685205 | c.503G > C | p.R168P | Exon 2 | Unknown | Uncertain significance | Possibly damaging (0.795) | |
| 6 | – | c.539_543delACTTC | p.F181Dfs*6 | Exon 2 | NR | NR | – | |
| 7 | rs143523371 | c.546G > T | p.T182 = | Exon 2 | Potentially mild | Likely pathogenic | – | |
| 8 | rs756024023 | c.546 + 5G > T | – | Intron 2 | Unknown | Conflicting interpretations of pathogenicity | – | |
| 14 | – | c.547-27A > G | – | Intron 2 | NR | NR | ## | |
| 21 | rs200856561 | c.752C > T | p.S251L | Exon 4 | Presumably non-pathogenic | Conflicting interpretations of pathogenicity | Benign (0.004) | |
| 22 | rs577915581 | c.761C > T | p.S254L | Exon 4 | Pathogenic/Likely pathogenic | Probably damaging (0.997) | ||
| 23 | rs1555599667 | c.796C > T | p.P266S | Exon 4 | Potentially mild | Likely pathogenic | Benign (0.001) | |
| 28 | – | c.1082C > A | p.P361Q | Exon 7 | Potentially less severe | NR | Probably damaging (1.000) | |
| 29 | rs142752477 | c.1124G > A | p.R375H | Exon 7 | Unknown | Uncertain significance | Probably Damaging (1.000) | |
| 31 | – | c.1170delC | p.N390Kfs*2 | Exon 7 | NR | NR | – | |
| 32 | rs776008078 | c.1190C > T | p.P397L | Exon 7 | Less severe | Uncertain significance | Probably damaging (1.000) | |
| 35 | – | c.1244C > T | p.T415M | Exon 8 | Potentially less severe | NR | Probably damaging (1.000) | |
| 36 | rs770610356 | c.1309C > T | p.R437C | Exon 8 | Less severe | Pathogenic/likely pathogenic | Probably damaging (0.995) | |
| 37 | rs747610090 | c.1316 T > A | p.M439K | Exon 8 | Potentially mild | Pathogenic/likely pathogenic | Benign (0.096) | |
| 43 | – | c.1494G > A | p.W498* | Exon 10 | Very severe | NR | – | |
| 46 | – | c.1562A > T | p.E521V | Exon 11 | Unknown | Uncertain significance | Probably damaging (1.000) | |
| 50 | rs747150965 | c.1669A > T | p.I557F | Exon 12 | Very severe | Conflicting interpretations of pathogenicity | Benign (0.069) | |
| 52 | rs764670084 | c.1798C > T | p.R600C | Exon 13 | Less severe | Pathogenic | probably damaging (1.000) | |
| 53 | rs914396317 | c.1857C > G | p.S619R | Exon 13 | Less severe | Likely pathogenic | Probably damaging (1.000) | |
| 55 | rs28940868 | c.1935C > A | p.D645E | Exon 14 | Potentially less severe | Pathogenic | Probably damaging (1.000) | |
| 56 | rs1555601633 | c.2003A > G | p.Y668C | Exon 14 | Potentially less severe | Uncertain significance | Probably damaging (1.000) | |
| 58 | – | c.2055C > G | p.Y685* | Exon 15 | Very severe | NR | – | |
| 62 | rs121907938 | c.2173C > T | p.R725W | Exon 15 | Less severe | Pathogenic | Probably damaging (1.000) | |
| 64 | rs1800312 | c.2238G > C | p.W746C | Exon 16 | Potentially mild | Pathogenic/likely pathogenic | Probably damaging (1.000) | |
| 71 | rs121907943 | c.2560C > T | p.R854* | Exon 18 | Very severe | Pathogenic | – | |
| 72 | rs192679574 | c.2647-7G > A | – | Intron 18 | Potentially mild | Pathogenic/likely pathogenic | – | |
| non-pathogenic variants | 1 | – | c.-260G > C | – | Exon 1 | Non-pathogenic | Likely benign | – |
| 3 | – | c.324 T > C | p.C108 = | Exon 2 | Non-pathogenic | Benign | – | |
| 9 | rs34746710 | c.546 + 293G > A | – | Intron 2 | Non-pathogenic | Benign | – | |
| 10 | rs8065426 | c.547-243C > G | – | Intron 2 | Non-pathogenic | Benign | – | |
| 11 | rs12452263 | c.547-238 T > C | – | Intron 2 | Non-pathogenic | Benign | – | |
| 12 | – | c.547-67C > G | – | Intron 2 | Non-pathogenic | Benign | – | |
| 13 | rs12452721 | c.547-39 T > G | – | Intron 2 | Non-pathogenic | Benign | – | |
| 15 | rs3816256 | c.547-4C > G | – | Intron 2 | non-pathogenic | benign | – | |
| 16 | rs1042393 | c.596A > G | p.H199R | Exon 3 | Non-pathogenic | Benign | 0.000 (benign) | |
| 17 | rs1042395 | c.668G > A | p.R223H | Exon 3 | Non-pathogenic | Benign | 0.206 (benign) | |
| 18 | – | c.692 + 38C > T | – | Intron 3 | Non-pathogenic | NR | – | |
| 19 | rs11150844 | c.693-216 T > C | – | Intron 3 | Non-pathogenic | Benign | – | |
| 20 | rs2304846 | c.705G > A | p.T235 = | Exon 4 | Unknown | Conflicting interpretations of pathogenicity | – | |
| 24 | – | c.858 + 5_858 + 6ins7GCAGCGG | – | Intron 4 | Unknown | NR | – | |
| 25 | rs5822325 | c.858 + 8G > A | – | Intron 4 | NR | Benign/likely benign | – | |
| 26 | rs2304845 | c.858 + 30 T > C | – | Intron 4 | Non-pathogenic | Benign | – | |
| 27 | rs2252455 | c.955 + 12G > A | – | Intron 5 | Non-pathogenic | Benign | – | |
| 30 | rs111832449 | c.1143C > G | p.T381 = | Exon 7 | NR | Conflicting interpretations of pathogenicity | – | |
| 33 | – | c.1194 + 19_1194 + 20insA | – | Intron 7 | NR | NR | – | |
| 34 | rs1800304 | c.1203G > A | p.Q401 = | Exon 8 | Non-pathogenic | Benign | – | |
| 38 | rs6565641 | c.1327-269A > G | – | Intron 8 | Non-pathogenic | Benign | – | |
| 39 | rs2278620 | c.1327-179G > A | – | Intron 8 | Non-pathogenic | Benign | – | |
| 40 | rs2278619 | c.1327-18A > G | – | Intron 8 | Non-pathogenic | Benign | – | |
| 41 | rs2278618 | c.1438-220A > G | – | Intron 9 | Non-pathogenic | Benign | – | |
| 42 | rs2304844 | c.1438-19G > C | – | Intron 9 | Non-pathogenic | Benign | – | |
| 44 | rs2304843 | c.1551 + 49C > A | – | Intron 10 | Non-pathogenic | Benign | – | |
| 45 | – | c.1552-52C > A | – | Intron 10 | NR | NR | # | |
| 47 | rs1042396 | c.1581G > A | p.R527 = | Exon 11 | Non-pathogenic | Benign | – | |
| 48 | rs2304842 | c.1636 + 43G > T | – | Intron 11 | Non-pathogenic | Benign | – | |
| 49 | rs79487884 | c.1636 + 210G > A | – | Intron 11 | Non-pathogenic | Benign | – | |
| 51 | rs1800307 | c.1726G > A† | p.G576S | Exon 12 | Presumably non-pathogenic | Benign | Probably damaging (1.000) | |
| 54 | rs2304837 | c.1888 + 21G > A | – | Intron 13 | Non-pathogenic | Benign | – | |
| 57 | rs2304836 | c.2040 + 20A > G | – | Intron 14 | Non-pathogenic | Benign | – | |
| 59 | – | c.2065G > A† | p.E689K | Exon 15 | Non-pathogenic | Benign, other | 0.092 (benign) | |
| 60 | rs1555601773 | c.2132C > G | p.T711R | Exon 15 | Non-pathogenic | Conflicting interpretations of pathogenicity | 0.999 | |
| (Probably damaging) | ||||||||
| 61 | rs1800310 | c.2133A > G | p.T711 = | Exon 15 | Non-pathogenic | Benign | – | |
| 63 | rs7221604 | c.2189 + 263G > A | – | Intron 15 | Non-pathogenic | Benign | – | |
| 65 | rs2304832 | c.2331 + 20G > A | – | Intron 16 | Non-pathogenic | Benign | – | |
| 66 | rs2304831 | c.2331 + 24 T > C | – | Intron 16 | Non-pathogenic | Likely benign | – | |
| 67 | rs2304830 | c.2332-198A > T | – | Intron 16 | Non-pathogenic | Benign | ||
| 68 | rs1126690 | c.2338G > A | p.V780I | Exon 17 | Non-pathogenic | Benign | 0.000 (benign) | |
| 69 | rs1800314 | c.2446G > A | p.V816I | Exon 17 | Non-pathogenic | Benign | 0.008 (benign) | |
| 70 | rs1042397 | c.2553G > A | p.G851 = | Exon 18 | Non-pathogenic | benign | – | |
| 73 | rs9890469 | c.2800-227C > T | – | Intron 19 | Non-pathogenic | benign | – | |
| 74 | – | c.2859G > A | p.*953 = | Exon 20 | NR | NR | # | |
| 75 | rs1800317 | c.*3G > A | – | Exon 20 | Non-pathogenic | Benign | – | |
| 76 | rs865903736 | c.*139dup | – | Exon 20 | NR | Likely benign | – | |
| 77 | rs8132 | c.*223C > T | – | Exon 20 | Non-pathogenic | Benign | – | |
| 78 | rs7567 | c.*419G > T | – | Exon 20 | NR | Benign | – | |
NR, not registered
†Pseudodeficiency alleles; Human Splicing Finder: #No impact on splicing; ##Potential alteration of splicing