Table 2

- Variants identified by targeted ATP7B gene sequencing by next-generation sequencing arranged by frequency.

#	Nucleotide change	Amino acid change	Variant effect	Variant classification by ClinVar	Region Exon/intron	Location on chromosome 13	dbSNP code	No. of alleles
1	c.3305T>C	p.Ile1102Thr	Missense	Pathogenic	15	52516629	560952220	4
2	c.956delC	p.Pro319HisfsTer44	Frameshift	Pathogenic	2	52548399	753674382	4
3	c.3741-3742 dupCA	p.Lys1248ThrfsTer83	Frameshift	Pathogenic	18	52511772	1462451206	3
4	c.3694A>C	p.Thr1232Pro	Missense	Likely pathogenic	17	52513192	568009639	3
5	c.4309A>T	p.Lys1437Ter	Stop-gain	Pathogenic	21	52508981	768833241	2
6	c.2575+1G>C	-	Splice-donor	Pathogenic	Intron 10	52524407	766149114	2
7	c.4021G>A	p.Gly1341Ser	Missense	Likely pathogenic	19	52511412	587783317	2
8	c.2336G>A	p.Trp779Ter	Stop-gain	Pathogenic	8	52532466	137853283	2
9	c.2866-2A>C	-	Splice-acceptor	Pathogenic	Intron 12	52520616	1377418826	2
10	c.2905C>T	p.Arg969Trp	Missense	Likely pathogenic	13	52520575	774028495	2
11	c.3061-12T>A	-	Intronic	Pathogenic	Intron 13	52518439	1045194246	2
12	c.2987T>C	p.Met996Thr	Missense	Pathogenic	13	52520493	770782111	2
13	c.2304dupC	p.Met769HisfsTer26	Frameshift	Pathogenic	8	52532497	193922103	2
14	c.4092-4093 delGT	p.Ser1365CysfsTer12	Frameshift	Likely pathogenic	20	52509759	747301758	2
15	c.3443T>C	p.Ile1148Thr	Missense	Pathogenic	16	52515330	60431989	2
16	c.3547-3548 delGC	p.Ala1183TyrfsTer2	Frameshift	Pathogenic	16	52515224	765139243	2
17	c.4022G>A	p.Gly1341Asp	Missense	Pathogenic	20	52509831	779494870	2
18	c.3263T>A	p.Leu1088Ter	Stop-gain	Pathogenic	15	52516671	753250853	2
19	c.2297C>G	p.Thr766Arg	Missense	Pathogenic	8	52532505	121907997	2
20	c.2827G>A	P.Gly943Ser	Missense	Pathogenic	12	52523836	28942076	2
21	c.2447+11delG	-	Intronic	Likely pathogenic	Intron 9, 11bp from exon 9	52531640	758601871	1
22	c.4051C>T	p.Gln1351Ter	Stop gain	Pathogenic	20	52509802	786204578	1
23	c.3517G>A	p.Glu1173Lys	Missense	Pathogenic	16	52515256	756029120	1
24	c.1924G>C	p.Asp642His	Missense	Pathogenic	6	52535995	72552285	1
25	c.1870-39T>C	-	Intronic	Likely pathogenic	Intron 5, 38 bp from exon 6	52536088	747432408	1
26	c.2663C>T	p.Thr888Ile	Missense	Likely pathogenic	11	52524210	935426164	1
27	c.1745-1746delTA	p.Ile582ArgfsTer25	Frameshift	Pathogenic	5	52539130	753962912	1
28	c.2332C>G	p.Arg778Gly	Missense	Pathogenic	8	52532470	137853284	1
29	c.562C>T	p.Gln188Ter	Stop-gain	Pathogenic	2	52548794	1412593296	1
30	c.2426G>A	p.Gly809Asp	Missense	VUS	9	52531673	762578415	1
31	c.1870-39T>G	-	Intronic	Not reported in ClinVar. Found in low % in ExAC	Intron 5, 39bp from exon 6	52536088	747432408	1
32	c.3556G>A	p.Gly1186Ser	Missense	Pathogenic	16	52515217	786204547	1
33	c.2002A>G	P.Met668Val	Missense	Conflicting (VUS / Likely pathogenic)	7	52534403	587783301	1
34	c.3955C>T	p.Arg1319Ter	Stop gain	Pathogenic	19	52511478	193922109	1
35	c.3472-3482delGGTTTAACCAT	p.Gly1158phefsTer	Frameshift	Pathogenic	Gross deletion	52515290	-	1
36	c.3538A>G	p.Ile1180Val	Missense	Likely pathogenic	16	52515235	1324203873	1
37	c.2730+39-2730+41delGTT	-	Intronic deletion	Likely pathogenic	Intron 11, 41bp from exon 11	52524101	751433161	1
38	c.2513delA	Lys838SerfsTer35	Frameshift	Pathogenic	10	52524469	777362050	1
39	c.314C>A	p.Ser105Ter	Stop gain	Pathogenic	2	52549042	753236073	1
40	c.3895C>T	p.Leu1299Phe	Missense	Pathogenic	18	52511620	749472361	1
41	c.2715G>C	p.Glu905Asp	Missense	VUS	11	52524158	923227127	1
42	c.3649-3654delGTTCTG	p.Val1217-Leu1218del	Inframe-deletion	Pathogenic	17	52513231	781266802	1
43	c.2804C>T	p.Thr935Met	Missense	Pathogenic	12	52523859	750019452	1
44	c.3960G>C	p.Arg1320Ser	Missense	Pathogenic	19	52511473	778732681	1
45	c.3121C>T	p.Arg1041Trp	Missense	Likely pathogenic	14	52518367	746485916	1
46	c.3836A>G	p.Asp1279Gly	Missense	Likely pathogenic	18	52511679	778914828	1
47	c.4114C>T	p.Gln1372Ter	Stop gain	Pathogenic	20	52509739	755584106	1
48	c.623C>T	p.Ala208Val	Missense	VUS but polyphen-2 possibly damaging; align-GVGD: Class C0)	2	52548733	754738204	1
49	c.3317T>A	p.Val1106Asp	Missense	Likely pathogenic	15	52516617	775541743	1
50	c.2606G>A	p.Gly869Glu	Missense	Likely pathogenic	11	52524267	775553302	1
51	c.2924C>A	p.Ser975Tyr	Missense	Pathogenic	13	52520556	778163447	1
52	c.2972C>T	p.Thr991Met	Missense	Pathogenic	13	52520508	41292782	1
53	c.2897T>G	p.Val966Gly	Missense	VUS by ACMG, SIFT: Damaging	13	52520583	761430052	1
54	c.1630C>T	p.Gln544Ter	Stop gain	Pathogenic	4	52542657	766906034	1
55	c.2576-44G>T	-	Intronic	VUS, previous analysis from invitae labs showed it is related to disease	Intron 10, 66bp from exon 10, 43bp from exon 11	52524341	746739918	1
56	c.3892G>A	p.V.1298Ile	Missense	VUS / SIFT: affect protein function	18	52511623	753044473	1
57	c.2507G>A	p.Gly836Glu	Missense	Likely pathogenic	10	52524476	773809011	1
58	c.915T>A	p.Cys305Ter	Stop gain	Pathogenic	2	52548441	398123137	1
59	c.347T>C	p.Ile116Thr	Missense	VUS Conflicting (Pathogenic by invitae)	2	52549009	199773340	1
60	c.352G>A	p.Asp118Asn	Missense	VUS by ACMG/SIFT is deleterious	2	52549004	769655497	1
61	c.1318A>G	p.Ser440Gly	Missense	VUS	3	52544853	759000301	1
62	c.1616C>T	p.pro539Leu	Missense	VUS / Likely pathogenic by ACMG	4	52542671	572122562	1
63	c.3646G>A	p.Val1216Met	Missense	Likely pathogenic	17	52513240	776280797	1
64	c.2807T>A	p.Leu936Ter	Stop gain	Pathogenic	12	52523856	776002066	1
65	c.4125-1G>A	-	Splice-acceptor	VUS / Suspicious for pathogenicity	Intron 20	52509166	1293549383	1
66	c.3182G>A	p.Gly1061Glu	Missense	Pathogenic	14	52513806	764131178	1
67	c.1924G>T	p.Asp642Tyr	Missense	Pathogenic	6	52535995	72552285	1
68	c.1934T>G	p.Met645Arg	Missense	Likely pathogenic	6	52535985	121907998	1
69	c.2530A>T	p.Lys844Ter	Stop gain	Pathogenic	10	52524453	780292767	1
70	c.2532delA	p.Val845SerfsTer28	Frameshift	Pathogenic	10	52524450	755709270	1
71	c.1708-1G>A	-	Splice acceptor	Pathogenic	Intron4	52539170	137853280	1
72	c.1543+1G>C	-	Splice donor	Pathogenic	intron3	52544627	1360279134	1
73	c.2333G>T	p.Arg778Leu	Missense	Pathogenic	8	52532469	28942074	1
74	c.2930C>T	p.Thr977Met	Missense	Pathogenic	13	52520550	72552255	1
75	c.2549C>T	p.Thr850Ile	Missense	Pathogenic	10	52524434	777629392	1
76	c.2000T>A	p.Leu667Ter	Stop gain	Likely pathogenic	7	52534405	1474837260	1

VUS: variant of uncertain significance, SIFT: Sorting Tolerant From Intolerant, #: number