Table 1.
Spectrum of mutations in the ATP7B gene of a large-scale sample of Chinese patients with Wilson’s disease
| Exon | Nucleotide mutation | Amino acid change | Mutation type | Domain | Allelic frequency in southern cohort | Allelic frequency in large-scale cohort | Pathogenicity | |
|---|---|---|---|---|---|---|---|---|
| PolyPhen-2 Score | Variant classification | |||||||
| 2 | c.121A>G | p.Asn41Asp | Missense | Before Cu1 | 0 | 0.04% (1/2604) | 0.029 | Uncertain significance |
| 2 | c.254G>T | p.Gly85Val | Missense | Cu1 | 0 | 0.04% (1/2604) | ||
| 2 | c.268_271DEL | p.Lys90PhefsX10 | Deletion | Cu1 | 0 | 0.04% (1/2604) | NA | Pathogenic |
| 2 | c.287A>G | p.Asp96Gly | Missense | Cu1 | 0 | 0.31% (8/2604) | ||
| 2 | c.314C>A | p.Ser105X | Nonsense | Cu1 | 0 | 0.15% (4/2604) | ||
| 2 | c.367DELG | p.Ala123ProfsX30 | Deletion | Cu1 | 0 | 0.04% (1/2604) | NA | Pathogenic |
| 2 | c.433G>T | p.Val145Phe | Missense | Cu2 | 0 | 0.08% (2/2604) | ||
| 2 | c.523INSA | NA | Insertion | Cu2 | 0 | 0.08% (2/2604) | NA | NA |
| 2 | c.525DupA | p.Val176SerfsX28 | Insertion | Cu2 | 0.50% (1/202) | 1.11% (29/2604) | ||
| 2 | c.588C>A | p.Asp196Glu | Missense | Cu2 | 0.99% (2/202) | 0.35% (9/2604) | ||
| 2 | c.592A>G | p.Arg198Gly | Missense | Cu2 | 0 | 0.04% (1/2604) | 0.735 | NA |
| 2 | c.685insA | NA | Insertion | Cu3 | 0 | 0.04% (1/2604) | ||
| 2 | c.695DELC | p.Pro232GlnfsX30 | Deletion | Cu3 | 0 | 0.04% (1/2604) | NA | Likely benign |
| 2 | c.748G>A | p.Gly250Arg | Missense | Cu3 | 0 | 0.04% (1/2604) | 0.004 | NA |
| 2 | c.813DELC | p.Cys271TrpfsX3 | Deletion | Cu3 | 0 | 0.04% (1/2604) | ||
| 2 | c.898_902DEL AAGTA | NA | Deletion | Cu3 | 0 | 0.04% (1/2604) | NA | NA |
| 2 | c.994G>T | p.Glu332X | Nonsense | bet Cu3/Cu4 | 0 | 0.42% (11/2604) | ||
| 2 | c.1057DELC | p.Gln353ArgfsX10 | Deletion | bet Cu3/Cu4 | 0 | 0.04% (1/2604) | NA | NA |
| 2 | c.1162C>T | p.GIn388X | Nonsense | Cu4 | 0 | 0.04% (1/2604) | ||
| 2 | c.1168A>G | p.Ile390Val | Missense | Cu4 | 0 | 0.58% (15/2604) | 0.019 | NA |
| 2 | c.EX2 DEL | NA | Deletion | Cu4 | 0 | 0.08% (2/2604) | ||
| 3 | c.1366G>C | p.Val456Leu | Missense | bet Cu4/Cu5 | 0 | 0.08% (2/2604) | ||
| 3 | c.1403_1416DEL | p.Ala468GlyfsX33 | Deletion | bet Cu4/Cu5 | 0 | 0.04% (1/2604) | NA | NA |
| 3 | c.1426G>A | p.Ala476Thr | Missense | bet Cu4/Cu5 | 0 | 0.04% (1/2604) | 0.002 | Likely benign |
| 3 | c.1448_1455DEL GAGCAGTG | p.Arg483SerfsX20 | Deletion | Cu5 | 0 | 0.04% (1/2604) | ||
| 3 | c.1449_1456DEL | p.Arg483SerfsX20 | Deletion | Cu5 | 0 | 0.08% (2/2604) | NA | NA |
| 3 | c.1470C>A | p.Cys490X | Nonsense | Cu5 | 0.50% (1/202) | 0.38% (10/2604) | ||
| 3 | c.1492A>T | p.Thr498Ser | Missense | Cu5 | 0 | 0.04% (1/2604) | ||
| 3 | c.1510_1511INSA | NA | Insertion | Cu5 | 0.50% (1/202) | 0.04% (1/2604) | NA | NA |
| 3 | c.1516_1517DELAT | NA | Deletion | Cu5 | 0 | 0.04% (1/2604) | ||
| 3 | c.1531C>T | p.Gln511X | Nonsense | Cu5 | 0 | 1.38% (36/2604) | ||
| 4 | c.1544G>T | p.Gly515Val | Missense | Cu5 | 0 | 0.04% (1/2604) | ||
| 4 | c.1545DELT | p.Gly515GlyfsX9 | Deletion | Cu5 | 0 | 0.04% (1/2604) | NA | NA |
| 4 | c.1552_1553DELTC | p.Ser518ArgfsX15 | Deletion | Cu5 | 0 | 0.04% (1/2604) | NA | NA |
| 4 | c.1639C>T | p.Gln547X | Nonsense | Cu5 | 0 | 0.04% (1/2604) | ||
| 5 | c.1745_1746DEL TA | NA | Deletion | Cu6 | 0 | 0.04% (1/2604) | NA | NA |
| 5 | c.1760C>T | p.Thr587Met | Missense | Cu6 | 0 | 0.04% (1/2604) | 0.005 | Likely benign |
| 5 | c.1782T>A | p.Tyr594X | Nonsense | Cu6 | 0 | 0.04% (1/2604) | NA | NA |
| 5 | c.1802DELC | NA | Deletion | Cu6 | 0 | 0.04% (1/2604) | NA | Pathogenic |
| 5 | c.1803DELC | p.Ser602AlafsX46 | Deletion | Cu6 | 0 | 0.04% (1/2604) | ||
| 5 | c.1817T>G | p.Val606Gly | Missense | Cu6 | 0 | 0.08% (2/2604) | ||
| 5 | c.1820DUPA | p.Phe608ValfsX2 | Insertion | Cu6 | 0 | 0.08% (2/2604) | ||
| 5 | c.1831G>A | p.Glu611Lys | Missense | Cu6 | 0 | 0.04% (1/2604) | ||
| 5 | c.1846C>T | p.Arg616Trp | Missense | Cu6 | 0 | 0.04% (1/2604) | ||
| 6 | c.1875_1876INS AATT | NA | Insertion | Cu6 | 0 | 0.04% (1/2604) | ||
| 6 | c.1925A>G | p.Asp642Gly | Missense | bet Cu6/TM1 | 0 | 0.04% (1/2604) | 0.899 | NA |
| 7 | c.1950G>A | p.Trp650X | Nonsense | bet Cu6/TM1 | 0 | 0.04% (1/2604) | ||
| 7 | c.1994T>G | p.Met665Arg | Missense | TM1 | 0 | 0.04% (1/2604) | 0.836 | NA |
| 7 | c.2012_2013INS ATAT | NA | Insertion | TM1 | 0 | 0.04% (1/2604) | NA | NA |
| 7 | c.2038C>T | p.Gln680X | Nonsense | bet TM1/TM2 | 0.50% (1/202) | 0.12% (3/2604) | ||
| 7 | c.2043DELC | p.Ser681SerfsX15 | Deletion | bet TM1/TM2 | 0 | 0.04% (1/2604) | NA | NA |
| 7 | c.2075T>C | p.Leu692Pro | Missense | TM2 | 0.50% (1/202) | 0.08% (2/2604) | 0.996 | NA |
| 7 | c.2078C>G | p.Ser693Cys | Missense | TM2 | 0.50% (1/202) | 0.15% (4/2604) | ||
| 7 | c.2097_2099DELCTT | p.Phe700del | Deletion | TM2 | 0 | 0.08% (2/2604) | ||
| 7 | c.2120A>G | p.Gln707Arg | Missense | TM2 | 0 | 0.04% (1/2604) | ||
| 8 | c.2128G>A | p.Gly710Ser | Missense | TM2 | 0 | 0.12% (3/2604) | ||
| 8 | c.2145C>A | p.Tyr715X | Nonsense | TM2 | 1.49% (3/202) | 0.12% (3/2604) | ||
| 8 | c.2156A>G | p.Tyr719Cys | Missense | bet TM2/TM3 | 0 | 0.04% (1/2604) | 0.990 | NA |
| 8 | c.2157C>A | p.Tyr719X | Nonsense | bet TM2/TM3 | 0 | 0.12% (3/2604) | NA | Pathogenic |
| 8 | c.2185A>G | p.Met729Val | Missense | bet TM2/TM3 | 0 | 0.04% (1/2604) | ||
| 8 | c.2192T>A | p.Val731Glu | Missense | TM3 | 0 | 0.08% (2/2604) | ||
| 8 | c.2195T>C | p.Leu732Pro | Missense | TM3 | 0 | 0.04% (1/2604) | ||
| 8 | c.2223T>A | p.Tyr741X | Nonsense | TM3 | 0 | 0.04% (1/2604) | ||
| 8 | c.2231C>T | p.Ser744Phe | Missense | TM3 | 0 | 0.04% (1/2604) | 1.000 | Uncertain significance |
| 8 | c.2233C>A | p.Leu745Met | Missense | TM3 | 0.50% (1/202) | 0.04% (1/2604) | 0.786 | NA |
| 8 | c.2251G>T | p.Ala751Ser | Missense | TM3 | 0 | 0.04% (1/2604) | 0.831 | Uncertain significance |
| 8 | c.2261A>G | p.Glu754Gly | Missense | bet TM3/TM4 | 0 | 0.04% (1/2604) | 0.960 | Benign |
| 8 | c.2267C>G | p.Ala756Gly | Missense | bet TM3/TM4 | 0 | 0.04% (1/2604) | ||
| 8 | c.2293G>A | p.Asp765Asn | Missense | TM4 | 0 | 0.04% (1/2604) | ||
| 8 | c.2294A>G | p.Asp765Gly | Missense | TM4 | 1.49% (3/202) | 0.35% (9/2604) | ||
| 8 | c.2297C>T | p.Thr766Met | Missense | TM4 | 0 | 0.08% (2/2604) | ||
| 8 | c.2298INS C | NA | Insertion | TM4 | 0 | 0.08% (2/2604) | NA | NA |
| 8 | c.2299INSC | p.Pro767ArgfsX28 | Insertion | TM4 | 0 | 0.04% (1/2604) | NA | NA |
| 8 | c.2302DUPC | NA | Insertion | TM4 | 0 | 0.08% (2/2604) | ||
| 8 | c.2304DUPC | p.Met769HisfsX26 | Insertion | TM4 | 0 | 1.08% (28/2604) | ||
| 8 | c.2304DELC | p.Met769CysfsX38 | Deletion | TM4 | 0 | 0.04% (1/2604) | ||
| 8 | c.2305A>G | p.Met769Val | Missense | TM4 | 0 | 0.12% (3/2604) | ||
| 8 | c.2308C>T | p.Leu770Phe | Missense | TM4 | 0 | 0.08% (2/2604) | 1.000 | NA |
| 8 | c.2316_2317INS CTCTTTGTG | p.Val772insLeuPheVal | Insertion | TM4 | 0 | 0.04% (1/2604) | NA | Uncertain significance |
| 8 | c.2332C>T | p.Arg778Trp | Missense | TM4 | 0.99% (2/202) | 0.19% (5/2604) | ||
| 8 | c.2333G>T | p.Arg778Leu | Missense | TM4 | 18.81% (38/202) | 28.57% (744/2604) | ||
| 8 | c.2333G>A | p.Arg778Gln | Missense | TM4 | 0 | 1.42% (37/2604) | ||
| 8 | c.2336G>A | p.Trp779X | Nonsense | TM4 | 0 | 0.04% (1/2604) | ||
| 8 | c.2341G>A | p.Glu781Lys | Missense | TM4 | 0 | 0.04% (1/2604) | 0.998 | NA |
| 9 | c.2383C>T | p.Leu795Phe | Missense | bet TM4/Td | 0.50% (1/202) | 0.08% (2/2604) | ||
| 9 | c.2390C>T | p.Ser797Phe | Missense | bet TM4/Td | 0 | 0.04% (1/2604) | 0.999 | Uncertain significance |
| 10 | c.2455C>T | p.Gln819X | Nonsense | bet TM4/Td | 0 | 0.04% (1/2604) | ||
| 10 | c.2464DUPA | p.Met822AsnfsX32 | Insertion | bet TM4/Td | 0 | 0.19% (5/2604) | ||
| 10 | c.2506G>A | p.Gly836Arg | Missense | Td | 0 | 0.04% (1/2604) | 0.998 | NA |
| 10 | c.2509G>T | p.Gly837X | Nonsense | Td | 0 | 0.04% (1/2604) | ||
| 10 | c.2510DELG | p.Gly837GlufsX35 | Deletion | Td | 0 | 0.04% (1/2604) | ||
| 10 | c.2519C>T | p.Pro840Leu | Missense | Td | 0 | 0.04% (1/2604) | ||
| 10 | c.2525A>G | p.Asp842Gly | Missense | Td | 0 | 0.04% (1/2604) | 0.999 | NA |
| 10 | c.2549C>T | p.Thr850Ile | Missense | Td | 1.49% (3/202) | 0.23% (7/2604) | ||
| 10 | c.2561A>G | p.Glu854Gly | Missense | Td | 0 | 0.04% (1/2604) | 0.998 | NA |
| 10 | c.2564C>A | p.Ser855Tyr | Missense | Td | 0 | 0.04% (1/2604) | ||
| 11 | c.2587C>T | p.Pro863Ser | Missense | Td | 0 | 0.04% (1/2604) | 0.950 | Uncertain significance |
| 11 | c.2593_2594INS GTCA | NA | Insertion | Td | 0 | 0.04% (1/2604) | NA | NA |
| 11 | c.2605G>A | p.Gly869Arg | Missense | bet Td/TM5 | 0 | 0.15% (4/2604) | ||
| 11 | c.2620G>C | p.Ala874Pro | Missense | bet Td/TM5 | 0.50% (1/202) | 0.27% (7/2604) | ||
| 11 | c.2621C>T | p.Ala874Val | Missense | bet Td/TM5 | 0.50% (1/202) | 2.42% (63/2604) | ||
| 11 | c.2648_2649DEL | p.Val883AlafsX3 | Deletion | bet Td/TM5 | 0 | 0.04% (1/2604) | ||
| 11 | c.2659del G | p.Ala887LeufsX14 | Deletion | bet Td/TM5 | 0 | 0.04% (1/2604) | ||
| 11 | c.2662A>C | p.Thr888Pro | Missense | bet Td/TM5 | 1.49% (3/202) | 0.61% (16/2604) | ||
| 11 | c.2668G>A | p.Val890Met | Missense | bet Td/TM5 | 0 | 0.12% (3/2604) | ||
| 12 | c.2740C>T | p.Gln914X | Nonsense | bet Td/TM5 | 0 | 0.04% (1/2604) | ||
| 12 | c.2755C>G | p.Arg919Gly | Missense | bet Td/TM5 | 2.97% (6/202) | 1.76% (46/2604) | ||
| 12 | c.2755C>T | p.Arg919Trp | Missense | bet Td/TM5 | 0 | 0.08% (2/2604) | ||
| 12 | c.2761A>C | p.Ser921Arg | Missense | bet Td/TM5 | 0 | 0.04% (1/2604) | ||
| 12 | c.2785A>G | p.Ile929Val | Missense | TM5 | 0 | 0.04% (1/2604) | ||
| 12 | c.2790_2792DEL | p.Ile930DEL | Deletion | TM5 | 0 | 0.23% (6/2604) | NA | Likely pathogenic |
| 12 | c.2794_2795INSGT | p.Ser932CysfsX4 | Insertion | TM5 | 0 | 0.04% (1/2604) | NA | NA |
| 12 | c.2804C>T | p.Thr935Met | Missense | TM5 | 2.97% (6/202) | 4.45% (116/2604) | ||
| 12 | c.2810DELT | p.Val937GlyfsX5 | Deletion | TM5 | 0 | 0.46% (12/2604) | ||
| 12 | c.2827G>A | p.Gly943Ser | Missense | TM5 | 00 | 0.27% (7/2604) | ||
| 12 | c.2828G>A | p.Gly943Asp | Missense | TM5 | 0.50% (1/202) | 2.04% (53/2604) | ||
| 12 | c.2848G>T | p.Val950Phe | Missense | bet TM5/TM6 | 0 | 0.04% (1/2604) | 0.978 | NA |
| 12 | c.2853_2856DEL | p.Gln951HisfsX15 | Deletion | bet TM5/TM6 | 0 | 0.04% (1/2604) | NA | Pathogenic |
| 13 | c.2885DELC | NA | Deletion | bet TM5/TM6 | 0 | 0.04% (1/2604) | NA | NA |
| 13 | c.2887C>T | p.Gln963X | Nonsense | bet TM5/TM6 | 0 | 0.04% (1/2604) | ||
| 13 | c.2905C>T | p.Arg969Trp | Missense | TM6 | 0 | 0.04% (1/2604) | ||
| 13 | c.2906G>A | p.Arg969gGln | Missense | TM6 | 0.99% (2/202) | 0.12% (3/2604) | ||
| 13 | c.2924C>A | p.Ser975Tyr | Missense | TM6 | 0.50% (1/202) | 0.77% (20/2604) | ||
| 13 | c.2930C>T | p.Thr977Met | Missense | TM6 | 0 | 0.08% (2/2604) | ||
| 13 | c.2939G>A | p.Cys980Tyr | Missense | TM6 | 0.50% (1/202) | 0.12% (3/2604) | ||
| 13 | c.2944G>A | p.Ala982Thr | Missense | TM6 | 0 | 0.04% (1/2604) | ||
| 13 | c.2957C>T | p.Ser986Phe | Missense | TM6 | 0 | 0.08% (2/2604) | ||
| 13 | c.2975C>T | p.Pro992Leu | Missense | bet TM6/Ph | 13.37% (27/202) | 13.02% (339/2604) | ||
| 13 | c.3007G>A | p.Ala1003Thr | Missense | bet TM6/Ph | 0.50% (1/202) | 0.19% (5/2604) | ||
| 13 | c.3008C>T | p.Ala1003Val | Missense | bet TM6/Ph | 0 | 0.04% (1/2604) | ||
| 13 | c.3010C>T | p.Gln1004X | Nonsense | bet TM6/Ph | 0 | 0.04% (1/2604) | NA | NA |
| 13 | c.3028A>G | p.Lys1010Glu | Missense | bet TM6/Ph | 0 | 0.04% (1/2604) | 0.997 | Uncertain significance |
| 13 | c.3029INST | p.Lys1010AsnfsX18 | Insertion | bet TM6/Ph | 0 | 0.08% (2/2604) | ||
| 13 | c.3029A>C | p.Lys1010Thr | Missense | bet TM6/Ph | 0 | 0.12% (3/2604) | ||
| 13 | c.3041C>T | p.Pro1014Leu | Missense | bet TM6/Ph | 0 | 0.04% (1/2604) | ||
| 13 | c.3044T>C | p.Leu1015Pro | Missense | bet TM6/Ph | 0 | 0.04% (1/2604) | 0.999 | NA |
| 13 | c.3053C>T | p.Ala1018Val | Missense | bet TM6/Ph | 0 | 0.12% (3/2604) | ||
| 13 | c.3056A>C | p.His1019Pro | Missense | bet TM6/Ph | 0 | 0.04% (1/2604) | 0.993 | NA |
| 14 | c.3083A>G | p.Lys1028Arg | Missense | Ph | 0 | 0.04% (1/2604) | 0.914 | NA |
| 14 | c.3085A>G | p.Thr1029Ala | Missense | Ph | 0.50% (1/202) | 0.04% (1/2604) | ||
| 14 | c.3087DELT | p.Gly1030AlafsX91 | Deletion | Ph | 0 | 0.04% (1/2604) | ||
| 14 | c.3089G>A | p.Gly1030Asp | Missense | Ph | 0 | 0.19% (5/2604) | ||
| 14 | c.3095T>C | p.Ile1032Thr | Missense | Ph | 0 | 0.04% (1/2604) | 0.997 | NA |
| 14 | c.3098C>T | p.Thr1033Ile | Missense | Ph | 0 | 0.04% (1/2604) | 0.999 | NA |
| 14 | c.3104G>T | p.Gly1035Val | Missense | Ph | 0 | 0.04% (1/2604) | ||
| 14 | c.3121C>T | p.Arg1041Trp | Missense | ATP loop | 0 | 0.08% (2/2604) | ||
| 14 | c.3122G>C | p.Arg1041Pro | Missense | ATP loop | 0 | 0.08% (2/2604) | ||
| 14 | c.3140A>T | p.Asp1047Val | Missense | ATP loop | 0 | 0.27% (7/2604) | ||
| 14 | c.3155C>T | p.Pro1052Leu | Missense | ATP loop | 0 | 0.12% (3/2604) | ||
| 14 | c.3157DUPC | p.Leu1053ProfsX16 | Insertion | ATP loop | 0 | 0.04% (1/2604) | ||
| 14 | c.3209C>G | p.Pro1070Arg | Missense | ATP loop | 0.50% (1/202) | 0.23% (6/2604) | 1.000 | NA |
| 14 | c.3221C>T | p.Ala1074Val | Missense | ATP loop | 0 | 0.04% (1/2604) | ||
| 14 | c.3236G>T | p.Cys1079Phe | Missense | ATP loop | 0 | 0.04% (1/2604) | ||
| 15 | c.3263T>C | p.Leu1088Ser | Missense | ATP loop | 0 | 0.15% (4/2604) | 1.000 | NA |
| 15 | c.3271T>C | p.Cys1091Arg | Missense | ATP loop | 0 | 0.04% (1/2604) | 0.960 | Uncertain significance |
| 15 | c.3274A>C | p.Thr1092Pro | Missense | ATP loop | 0 | 0.08% (2/2604) | 0.832 | NA |
| 15 | c.3284A>C | p.Gln1095Pro | Missense | ATP loop | 0 | 0.04% (1/2604) | ||
| 15 | c.3293C>G | p.Pro1098Arg | Missense | ATP loop | 0 | 0.04% (1/2604) | ||
| 15 | c.3307DELG | NA | Deletion | ATP loop | 0 | 0.04% (1/2604) | NA | NA |
| 15 | c.3310T>C | p.Cys1104Arg | Missense | ATP loop | 0 | 0.04% (1/2604) | ||
| 15 | c.3311G>A | p.Cys1104Tyr | Missense | ATP loop | 0 | 0.04% (1/2604) | ||
| 15 | c.3316G>A | p.Val1106Ile | Missense | ATP loop | 2.97% (6/202) | 1.08% (28/2604) | ||
| 15 | c.3368C>T | p.Pro1123Leu | Missense | ATP loop | 0 | 0.04% (1/2604) | 0.001 | Uncertain significance |
| 15 | c.3376DELC | p.His1126ThrfsX2 | Deletion | ATP loop | 0 | 0.04% (1/2604) | ||
| 15 | c.3377_3378DELAC | p.His1126ProfsX3 | Deletion | ATP loop | 0 | 0.12% (3/2604) | NA | NA |
| 16 | c.3426G>C | p.Gln1142His | Missense | ATP loop | 0.50% (1/202) | 1.04% (27/2604) | ||
| 16 | c.3443T>C | p.Ile1148Thr | Missense | ATP loop | 3.47% (7/202) | 3.19% (84/2604) | ||
| 16 | c.3445G>A | p.Gly1149Arg | Missense | ATP loop | 0 | 0.04% (1/2604) | 1.000 | Uncertain significance |
| 16 | c.3446G>C | p.Gly1149Ala | Missense | ATP loop | 0.50% (1/202) | 0.04% (1/2604) | ||
| 16 | c.3446G>A | p.Gly1149Glu | Missense | ATP loop | 0.50% (1/202) | 0.27% (7/2604) | ||
| 16 | c.3451C>G | p.Arg1151Gly | Missense | ATP loop | 0 | 0.04% (1/2604) | 1.000 | Uncertain significance |
| 16 | c.3451C>T | p.Arg1151Cys | Missense | ATP loop | 0 | 0.08% (2/2604) | ||
| 16 | c.3452G>A | p.Arg1151His | Missense | ATP loop | 0 | 0.19% (5/2604) | ||
| 16 | c.3459G>T | p.Trp1153Cys | Missense | ATP loop | 0.99% (2/202) | 0.19% (5/2604) | ||
| 16 | c.3502G>C | p.Ala1168Pro | Missense | ATP loop | 0 | 0.04% (1/2604) | ||
| 16 | c.3517G>A | p.Glu1173Lys | Missense | ATP loop | 0.50% (1/202) | 0.54% (14/2604) | ||
| 16 | c.3532A>G | p.Thr1178Ala | Missense | ATP loop | 4.95% (10/202) | 0.77% (20/2604) | ||
| 17 | c.3563T>G | p.Leu1188Arg | Missense | ATP loop | 0 | 0.04% (1/2604) | 0.998 | NA |
| 17 | c.3577G>C | p.Ala1193Pro | Missense | ATP loop | 0 | 0.04% (1/2604) | ||
| 17 | c.3584C>T | p.Ala1195Val | Missense | ATP loop | 0 | 0.04% (1/2604) | 0.997 | Pathogenic |
| 17 | c.3587A>G | p.Asp1196Gly | Missense | ATP loop | 0 | 0.04% (1/2604) | 1.000 | NA |
| 17 | c.3605C>G | p.Ala1202Gly | Missense | ATP loop | 0 | 0.08% (2/2604) | ||
| 17 | c.3646G>A | p.Val1216Met | Missense | ATP bind | 1.49% (3/202) | 1.34% (35/2604) | ||
| 17 | c.3653T>C | p.Leu1218Pro | Missense | ATP bind | 0 | 0.04% (1/2604) | 0.999 | NA |
| 17 | c.3659C>T | p.Thr1220Met | Missense | ATP bind | 0 | 0.04% (1/2604) | ||
| 17 | c.3677C>T | p.Thr1226Ile | Missense | ATP bind | 0.50% (1/202) | 0.08% (2/2604) | 0.990 | NA |
| 17 | c.3679G>C | p.Ala1227Pro | Missense | ATP bind | 0 | 0.04% (1/2604) | 0.999 | NA |
| 17 | c.3682A>T | p.Arg1228X | Nonsense | ATP bind | 0 | 0.04% (1/2604) | ||
| 18 | c.3700DELG | p.Val1234LeufsX96 | Deletion | ATP bind | 0 | 0.23% (6/2604) | NA | NA |
| 18 | c.3715G>T | p.Val1239Phe | Missense | ATP bind | 0 | 0.12% (3/2604) | 0.997 | NA |
| 18 | c.3716T>G | p.Val1239Gly | Missense | ATP bind | 0.50% (1/202) | 0.04% (1/2604) | ||
| 18 | c.3733C>G | p.Pro1245Ala | Missense | ATP hinge | 0 | 0.04% (1/2604) | 1.000 | Uncertain significance |
| 18 | c.3741C>G | p.His1247Gln | Missense | ATP hinge | 0 | 0.04% (1/2604) | ||
| 18 | c.3744G>C | p.Lys1248Asn | Missense | ATP hinge | 0 | 0.08% (2/2604) | ||
| 18 | c.3766_3767DUPCA | p.Gln1256ProfsX75 | Insertion | ATP hinge | 0 | 0.04% (1/2604) | NA | Pathogenic |
| 18 | c.3767INSCA | NA | Insertion | ATP hinge | 0 | 0.08% (2/2604) | NA | Pathogenic |
| 18 | c.3776G>T | p.Gly1259Val | Missense | ATP hinge | 0 | 0.12% (3/2604) | 0.988 | NA |
| 18 | c.3791T>C | p.Met1264Thr | Missense | ATP hinge | 0 | 0.04% (1/2604) | 0.990 | NA |
| 18 | c.3793G>T | p.Val1265Leu | Missense | ATP hinge | 0.50% (1/202) | 0.04% (1/2604) | 0.980 | NA |
| 18 | c.3796G>C | p.Gly1266Arg | Missense | ATP hinge | 0 | 0.04% (1/2604) | 0.998 | NA |
| 18 | c.3799G>A | p.Asp1267Asn | Missense | ATP hinge | 0 | 0.04% (1/2604) | ||
| 18 | c.3802G>A | p.Gly1268Arg | Missense | ATP hinge | 0 | 0.04% (1/2604) | ||
| 18 | c.3809A>G | p.Asn1270Ser | Missense | ATP hinge | 1.98% (4/202) | 1.88% (49/2604) | ||
| 18 | c.3818C>T | p.Pro1273Leu | Missense | ATP hinge | 0 | 0.08% (2/2604) | ||
| 18 | c.3818C>A | p.Pro1273Gln | Missense | ATP hinge | 0 | 0.15% (4/2604) | ||
| 18 | c.3824T>C | p.Leu1275Ser | Missense | ATP hinge | 0.50% (1/202) | 0.08% (2/2604) | 1.000 | NA |
| 18 | c.3836A>G | p.Asp1279Gly | Missense | ATP hinge | 0 | 0.19% (5/2604) | ||
| 18 | c.3843DUPT | p.Val1282CysfsX22 | Insertion | ATP hinge | 0 | 0.08% (2/2604) | ||
| 18 | c.3848C>T | p.Ala1283Val | Missense | ATP hinge | 0 | 0.04% (1/2604) | 1.000 | Uncertain significance |
| 18 | c.3851_3876DEL | NA | Deletion | ATP hinge | 0 | 0.08% (2/2604) | NA | NA |
| 18 | c.3859G>A | p.Gly1287Ser | Missense | ATP hinge | 0.99% (2/202) | 0.19% (5/2604) | ||
| 18 | c.3877G>A | p.Glu1293Lys | Missense | ATP hinge | 0 | 0.04% (1/2604) | ||
| 18 | c.3884C>T | p.Ala1295Val | Missense | bet ATP hinge/TM7 | 1.98% (4/202) | 0.61% (16/2604) | ||
| 18 | c.3889G>A | p.Val1297Ile | Missense | bet ATP hinge/TM7 | 0 | 0.04% (1/2604) | ||
| 18 | c.3896T>G | p.Leu1299Arg | Missense | bet ATP hinge/TM7 | 0 | 0.04% (1/2604) | 0.996 | NA |
| 18 | c.3901_3902INSA | p.Arg1301PhefsX3 | Insertion | bet ATP hinge/TM7 | 0 | 0.08% (2/2604) | NA | NA |
| 19 | c.3955C>T | p.Arg1319X | Nonsense | bet ATP hinge/TM7 | 0 | 0.15% (4/2604) | ||
| 19 | c.3960G>C | p.Arg1320Ser | Missense | bet ATP hinge/TM7 | 0.50% (1/202) | 0.12% (3/2604) | ||
| 19 | c.3965G>C | p.Arg1322Pro | Missense | bet ATP hinge/TM7 | 0.50% (1/202) | 0.04% (1/2604) | ||
| 19 | c.3982G>A | p.Ala1328Thr | Missense | TM7 | 0.99% (2/202) | 0.23% (6/2604) | ||
| 19 | c.4003G>C | p.Gly1335Arg | Missense | TM7 | 0 | 0.23% (6/2604) | ||
| 19 | c.4005_4006INS | p.Gly1335INS LXWVA | Insertion | TM7 | 0 | 0.08% (2/2604) | NA | NA |
| 20 | c.4043T>A | p.Ile1348Asn | Missense | TM7 | 0 | 0.04% (1/2604) | ||
| 20 | c.4057T>C | p.Trp1353Arg | Missense | TM8 | 0 | 0.08% (2/2604) | ||
| 20 | c.4059G>A | p.Trp1353X | Nonsense | TM8 | 0 | 0.04% (1/2604) | ||
| 20 | c.4064G>A | p.Gly1355Asp | Missense | TM8 | 0 | 0.15% (4/2604) | ||
| 20 | c.4094_4097DELCTGT | p.Ser1365TrpfsX27 | Deletion | TM8 | 0 | 0.04% (1/2604) | ||
| 20 | c.4112T>C | p.Leu1371Pro | Missense | TM8 | 0.50% (1/202) | 0.27% (7/2604) | ||
| 20 | c.4114C>T | p.Gln1372X | Nonsense | TM8 | 0.50% (1/202) | 0.42% (11/2604) | ||
| 21 | c.4162DELG | p.Ala1388ArgfsX5 | Deletion | after TM8 | 0 | 0.04% (1/2604) | ||
| 21 | c.4175T>A | p.Met1392Lys | Missense | after TM8 | 0 | 0.04% (1/2604) | ||
| 21 | c.4272T>G | p.Tyr1424X | Nonsense | after TM8 | 0 | 0.04% (1/2604) | NA | NA |
| 21 | c.4333G>C | p.Ala1445Pro | Missense | 3COOH | 0 | 0.04% (1/2604) | ||
TMS transmembrane domain, TDS transduction domain
Novel mutations are highlighted in bold