Causative variant profile of collagen VI-related dystrophy in Japan

Inoue, Michio; Saito, Yoshihiko; Yonekawa, Takahiro; Ogawa, Megumu; Iida, Aritoshi; Nishino, Ichizo; Noguchi, Satoru

doi:10.1186/s13023-021-01921-2

Orphanet Journal of Rare Diseases

Table 1. Causative variant profile of collagen VI-related dystrophy

From: Causative variant profile of collagen VI-related dystrophy in Japan

Family	Gene	Mono or Bi-allelic	Category	Domain	Nucleotide change	Protein change	Phenotype	COL6 IHC	Inheritance	Report
1	COL6A1	BA	Missense	C1	c.1879G>C homozygous	p.G627R	BM	Normal	Recessive	Novel
2-1^a	COL6A1	MA	Splicing	N1	c.428+1G>T	p.Y77_G143del	BM	SSCD	Dominant	[12]
2-2^a	COL6A1	MA	Splicing	N1	c.428+1G>T	p.Y77_G143del	BM	Normal	Dominant	[12]
3	COL6A1	MA	Large deletion	THD	c.589-7_804+490del	p.E197_E285del	Intermediate	SSCD	Dominant	Novel
4	COL6A1	MA	Large deletion	THD	c.589-7_804+490del	p.E197_E285del	UCMD	SSCD	de novo	Novel
5	COL6A1	MA	Large deletion	THD	c.765_903+26del	p.P254_K301del	UCMD	SSCD	de novo	Novel
6	COL6A1	MA	Glycine substitution	THD	c.806G>A	p.G269E	UCMD	SSCD	de novo	[28]
7	COL6A1	MA	Glycine substitution	THD	c.833G>A	p.G278E	Intermediate	SSCD	de novo	[11]
8	COL6A1	MA	Glycine substitution	THD	c.841G>A	p.G281R	Intermediate	Normal	de novo	[14]
9	COL6A1	MA	Small deletion	THD	c.845_847del	p.E282del	UCMD	SSCD	de novo	Novel
10	COL6A1	MA	Glycine substitution	THD	c.849G>A	p.G284R	UCMD	SSCD	Dominant	[14]
11	COL6A1	MA	Glycine substitution	THD	c.850G>A	p.G284R	UCMD	SSCD	de novo	[14]
12	COL6A1	MA	Glycine substitution	THD	c.850G>A	p.G284R	UCMD	SSCD	de novo	[14]
13	COL6A1	MA	Glycine substitution	THD	c.850G>A	p.G284R	UCMD	SSCD	de novo	[14]
14	COL6A1	MA	Glycine substitution	THD	c.850G>A	p.G284R	UCMD	SSCD	de novo	[14]
15	COL6A1	MA	Glycine substitution	THD	c.850G>A	p.G284R	UCMD	SSCD	de novo	[14]
16	COL6A1	MA	Glycine substitution	THD	c.859G>C	p.G287R	UCMD	NA	de novo	[35]
17	COL6A1	MA	Glycine substitution	THD	c.860G>A	p.G287E	UCMD	SSCD	de novo	Novel
18	COL6A1	MA	Glycine substitution	THD	c.868G>A	p.G290R	UCMD	SSCD	de novo	[38]
19	COL6A1	MA	Glycine substitution	THD	c.868G>A	p.G290R	UCMD	Normal	Dominant	[38]
20	COL6A1	MA	Glycine substitution	THD	c.868G>A	p.G290R	Intermediate	SSCD	de novo	[38]
21	COL6A1	MA	Glycine substitution	THD	c.868G>A	p.G290R	UCMD	SSCD	de novo	[38]
22	COL6A1	MA	Glycine substitution	THD	c.868G>A	p.G290R	Intermediate	NA	de novo	[14]
23	COL6A1	MA	Glycine substitution	THD	c.868G>A	p.G290R	Intermediate	SSCD	de novo	[14]
24	COL6A1	MA	Glycine substitution	THD	c.868G>A	p.G290R	UCMD	SSCD	de novo	[14]
25	COL6A1	MA	Glycine substitution	THD	c.868G>A	p.G290R	Intermediate	SSCD	de novo	[14]
26-1^b	COL6A1	MA	Glycine substitution	THD	c.877G>A	p.G293R	Intermediate	NA	Dominant	[35]
26-2^b	COL6A1	MA	Glycine substitution	THD	c.877G>A	p.G293R	Intermediate	NA	Dominant	[35]
26-3^b	COL6A1	MA	Glycine substitution	THD	c.877G>A	p.G293R	Intermediate	NA	Dominant	[35]
27	COL6A1	MA	Glycine substitution	THD	c.877G>A	p.G293R	UCMD	SSCD	de novo	[35]
28	COL6A1	MA	Glycine substitution	THD	c.877G>A	p.G293R	UCMD	NA	de novo	[35]
29	COL6A1	MA	Glycine substitution	THD	c.877G>A	p.G293R	Intermediate	SSCD	de novo	[35]
30-1^c	COL6A1	MA	Glycine substitution	THD	c.877G>A	p.G293R	BM	NA	Dominant	[35]
30-2^c	COL6A1	MA	Glycine substitution	THD	c.877G>A	p.G293R	BM	NA	Dominant	[35]
31	COL6A1	MA	Glycine substitution	THD	c.895G>A	p.G299R	Intermediate	SSCD	de novo	[35]
32	COL6A1	MA	Glycine substitution	THD	c.896G>A	p.G299E	Intermediate	SSCD	de novo	[23]
33	COL6A1	MA	Splicing	THD	c.930+189C>T	p.K310_G311insTRSTAPRRPLHLEGQGQPPRHPAK	UCMD	SSCD	de novo	[20]
34	COL6A1	MA	Splicing	THD	c.930+189C>T	p.K310_G311insTRSTAPRRPLHLEGQGQPPRHPAK	Intermediate	SSCD	de novo	[20]
35	COL6A1	MA	Splicing	THD	c.930+189C>T	p.K310_G311insTRSTAPRRPLHLEGQGQPPRHPAK	UCMD	SSCD	de novo	[20]
36	COL6A1	MA	Splicing	THD	c.930+189C>T	p.K310_G311insTRSTAPRRPLHLEGQGQPPRHPAK	UCMD	SSCD	de novo	[20]
37	COL6A1	MA	Splicing	THD	c.930+189C>T	p.K310_G311insTRSTAPRRPLHLEGQGQPPRHPAK	Intermediate	SSCD	de novo	[20]
38	COL6A1	MA	Splicing	THD	c.930+189C>T	p.K310_G311insTRSTAPRRPLHLEGQGQPPRHPAK	UCMD	SSCD	de novo	[20]
39	COL6A1	MA	Missense	THD	c.956A>G	p.K319R	Intermediate	SSCD	de novo	Novel
40-1^d	COL6A1	MA	Missense	THD	c.956A>G	p.K319R	BM	SSCD	Dominant	Novel
40-2^d	COL6A1	MA	Missense	THD	c.956A>G	p.K319R	BM	NA	Dominant	Novel
41-1^e	COL6A1	MA	Missense	THD	c.956A>G	p.K319R	BM	SSCD	Dominant	Novel
41-2^e	COL6A1	MA	Missense	THD	c.956A>G	p.K319R	BM	NA	Dominant	Novel
41-3^e	COL6A1	MA	Missense	THD	c.956A>G	p.K319R	BM	NA	Dominant	Novel
41-4^e	COL6A1	MA	Missense	THD	c.956A>G	p.K319R	BM	NA	Dominant	Novel
41-5^e	COL6A1	MA	Missense	THD	c.956A>G	p.K319R	BM	NA	Dominant	Novel
42	COL6A1	MA	Missense	THD	c.957G>T	p.K319N	UCMD	SSCD	de novo	[7]
43	COL6A1	MA	Splicing	THD	c.958-2A>T	p.G320_K334del	UCMD	SSCD	de novo	Novel
44	COL6A1	MA	Small deletion	THD	c.958_966del	p.G320_E322del	UCMD	SSCD	de novo	[7]
45	COL6A1	MA	Small deletion	THD	c.958_966del	p.G320_E322del	UCMD	SSCD	de novo	[7]
46	COL6A1	MA	Small deletion	THD	c.958_966del	p.G320_E322del	UCMD	SSCD	de novo	[7]
47	COL6A1	MA	Small deletion	THD	c.967_975del	p.K324_G326del	UCMD	SSCD	de novo	[7]
48	COL6A1	MA	Splicing	THD	c.1003-1G>A	p.G335_D352del	BM	SSCD	de novo	[39]
49	COL6A1	MA	Glycine substitution	THD	c.1022G>A	p.G341D	Intermediate	SSCD	de novo	[2]
50-1^f	COL6A1	MA	Glycine substitution	THD	c.1022G>A	p.G341D	BM	SSCD	Dominant	[2]
50-2^f	COL6A1	MA	Glycine substitution	THD	c.1022G>A	p.G341D	BM	NA	Dominant	[2]
51	COL6A1	MA	Glycine substitution	THD	c.1022G>T	p.G341V	BM	Normal	Dominant	[18]
52	COL6A1	MA	Splicing	THD	c.1056+1G>A	p.G335_D352del	Intermediate	SSCD	de novo	[30]
53	COL6A1	MA	Splicing	THD	c.1056+1G>A	p.G335_D352del	Intermediate	SSCD	de novo	[30]
54	COL6A1	MA	Splicing	THD	c.1056+1G>A	p.G335_D352del	Intermediate	SSCD	de novo	[30]
55-1^g	COL6A1	MA	Splicing	THD	c.1056+1G>A	p.G335_D352del	BM	Normal	Dominant	[30]
55-2^g	COL6A1	MA	Splicing	THD	c.1056+1G>A	p.G335_D352del	BM	NA	Dominant	[30]
56-1^h	COL6A1	MA	Splicing	THD	c.1056+1G>A	p.G335_D352del	BM	SSCD	Dominant	[30]
56-2^h	COL6A1	MA	Splicing	THD	c.1056+1G>A	p.G335_D352del	BM	NA	Dominant	[30]
57	COL6A1	MA	Splicing	THD	c.1056+3A>C	p.G335_D352del	BM	SSCD	de novo	[32]
58	COL6A1	MA	Glycine substitution	THD	c.1138G>A	p.G380R	UCMD	SSCD	de novo	Novel
59	COL6A1	MA	Glycine substitution	THD	c.1255G>A	p.G419S	BM	Normal	Dominant	Novel
60	COL6A1	MA	Splicing	THD	c.1461+4A>G	p.G467_E487del	UCMD	Normal	de novo	[28]
61	COL6A2	BA	Splicing Splicing	THD THD-C1	c.1270-1G>C c.1771-3C>G	p.G424_K444del p.G591fs	UCMD	CD	Recessive	[7]
62	COL6A2	BA	Splicing	THD	c.1572+1G>C homozygous	p.G508_P524del	UCMD	CD	Recessive	[7]
63	COL6A2	BA	Splicing Small deletion	THD C1	c.1770+5G>A c.2267_2272del	p.G562_T573del p.A756_I757del	UCMD	SSCD	Recessive	[13] [13]
64	COL6A2	BA	Splicing Small deletion	THD-C1 C1	c.1771-2A>T c.2279_2280del	p.G591fs p.D761fs	BM	CD	Recessive	[7]
65-1ⁱ	COL6A2	BA	Missense Missense	C1 C2	c.2093C>T c.2927T>C	p.A698V p.L976S	BM	SSCD	Recessive	Novel Novel
65-2ⁱ	COL6A2	BA	Missense Missense	C1 C2	c.2093C>T c.2927T>C	p.A698V p.L976S	BM	NA	Recessive	Novel Novel
66	COL6A2	BA	PTC Missense	C2	c.2386A>T c.2584C>T	p.K796X p.R862W	UCMD	SSCD	Recessive	Novel, [40]
67	COL6A2	BA	Small deletion	C1-C2 THD	c.2678_2700del homozygous	p.P893fs	UCMD	CD	Recessive	[7]
68	COL6A2	BA	Missense Small deletion	N1	c.2488C>T c.1487_1512del	p.R830W p.R498fs	BM	SSCD	Recessive	[5, 41]
69	COL6A2	MA	Missense	N1	c.167G>A	p.S56N	BM	SSCD	de novo	Novel
70	COL6A2	MA	Missense	THD	c.565G>A	p.A189T	BM	Normal	de novo	Novel
71	COL6A2	MA	Splicing	THD	c.736-1G>A	p.C246_K267del	UCMD	SSCD	de novo	[42]
72	COL6A2	MA	Glycine substitution	THD	c.785G>T	p.G262V	BM	SSCD	Dominant	Novel
73	COL6A2	MA	Splicing	THD	c.801+1G>T	p.C246_K267del	UCMD	SSCD	de novo	[16]
74	COL6A2	MA	Splicing	THD	c.801+2T>C	p.C246_K267del	UCMD	SSCD	de novo	[3]
75	COL6A2	MA	Glycine substitution	THD	c.802G>T	p.G268C	UCMD	SSCD	de novo	Novel
76	COL6A2	MA	Glycine substitution	THD	c.812G>A	p.G271D	Intermediate	SSCD	de novo	[7]
77	COL6A2	MA	Glycine substitution	THD	c.820G>A	p.G274S	Intermediate	SSCD	Dominant	Novel
78	COL6A2	MA	Glycine substitution	THD	c.821G>A	p.G274D	Intermediate	SSCD	de novo	Novel
79	COL6A2	MA	Glycine substitution	THD	c.838G>C	p.G280R	Intermediate	SSCD	de novo	Novel
80	COL6A2	MA	Glycine substitution	THD	c.839G>A	p.G280D	BM	SSCD	de novo	Novel
81	COL6A2	MA	Splicing	THD	c.855+1G>A	p.G268_Q285del	UCMD	SSCD	de novo	[35]
82	COL6A2	MA	Splicing	THD	c.856-2A>G	p.G286_K309del	UCMD	SSCD	Dominant	[7]
83-1^j	COL6A2	MA	Splicing	THD	c.856-2A>G	p.G286_K309del	BM	SSCD	Dominant	[7]
83-2^j	COL6A2	MA	Splicing	THD	c.856-2A>G	p.G286_K309del	BM	NA	Dominant	[7]
84	COL6A2	MA	Glycine substitution	THD	c.866G>A	p.G289D	BM	SSCD	Dominant	[8]
85	COL6A2	MA	Glycine substitution	THD	c.875G>T	p.G292V	UCMD	SSCD	de novo	[7]
86	COL6A2	MA	Glycine substitution	THD	c.893G>A	p.G298E	UCMD	SSCD	de novo	Novel
87	COL6A2	MA	Large deletion	THD	c.900+102_1000-43del	p.G301_K333del	UCMD	SSCD	de novo	Novel
88	COL6A2	MA	Glycine substitution	THD	c.901G>T	p.G301C	UCMD	SSCD	de novo	[7]
89	COL6A2	MA	Glycine substitution	THD	c.902G>T	p.G301V	Intermediate	SSCD	de novo	Novel
90	COL6A2	MA	Glycine substitution	THD	c.902G>A	p.G301D	UCMD	SSCD	de novo	[7]
91	COL6A2	MA	Glycine substitution	THD	c.902G>A	p.G301D	UCMD	SSCD	de novo	[7]
92	COL6A2	MA	Glycine substitution	THD	c.911G>T	p.G304V	BM	SSCD	de novo	Novel
93	COL6A2	MA	Missense	THD	c.943G>A	p.D315N	UCMD	SSCD	de novo	Novel
94	COL6A2	MA	Missense	THD	c.943G>A	p.D315N	BM	Normal	Dominant	Novel
95	COL6A2	MA	Splicing	THD	c.950_954+8del	p.G310_K318del	UCMD	SSCD	de novo	Novel
96	COL6A2	MA	Splicing	THD	c.955-2A>C	p.G319_K333del	UCMD	NA	de novo	Novel
97	COL6A2	MA	Splicing	THD	c.955-2A>G	p.G319_K333del	UCMD	SSCD	de novo	[14]
98	COL6A2	MA	Splicing	THD	c.955-2A>G	p.G319_K333del	Intermediate	SSCD	de novo	[14]
99-1^k	COL6A2	MA	Splicing	THD	c.1053+1G>A	p.G334_ R351del	BM	SSCD	Dominant	Novel
99-2^k	COL6A2	MA	Splicing	THD	c.1053+1G>A	p.G334_ R351del	BM	NA	Dominant	Novel
100	COL6A2	MA	Glycine substitution	THD	c.1664G>A	p.G555E	UCMD	SSCD	de novo	Novel
101	COL6A2	MA	Small deletion	C1	c.1858_1860del	p.I620del	UCMD	SSCD	de novo	Novel
102	COL6A2	MA	Missense	C1	c.1861G>A	p.D621N	BM	SSCD	Dominant	[2]
103	COL6A2	MA	Missense	C1	c.1870G>A	p.E624K	BM	Normal	de novo	[42]
104	COL6A2	MA	Missense	C1	c.2192C>G	p.T731R	BM	SSCD	de novo	Novel
105	COL6A2	MA	Glycine substitution	C1	c.2197G>A	p.G733R	BM	SSCD	de novo	[43]
106	COL6A2	MA	Missense	C1	c.2271C>G	p.I757M	BM	Normal	de novo	Novel
107	COL6A2	MA	Small deletion	C2	c.2741_2743del	p.F914del	BM	SSCD	de novo	Novel
108	COL6A2	MA	Missense	C2	c.2978G>A	p.R993H	BM	SSCD	de novo	Novel
109	COL6A3	BA	Small deletion Small deletion	N1 C3	c.5692delG c.8737delG	p.V1898fs p.A2913fs	UCMD	CD	Recessive	[7]
110	COL6A3	MA	Missense	N1	c.5525G>A	p.G1842E	BM	SSCD	Dominant	[12]
111	COL6A3	MA	Missense	N1	c.5525G>A	p.G1842E	BM	SSCD	Dominant	[12]
112-1^l	COL6A3	MA	Missense	N1	c.5525G>A	p.G1842E	BM	NA	Dominant	[12]
112-2^l	COL6A3	MA	Missense	N1	c.5525G>A	p.G1842E	BM	NA	Dominant	[12]
113	COL6A3	MA	Missense	THD	c.5525G>A	p.G1842E	BM	Normal	Dominant	[12]
114	COL6A3	MA	Splicing	THD	c.6157-2A>G	p.G2053_P2070del	UCMD	SSCD	de novo	[7]
115	COL6A3	MA	Splicing	THD	c.6157-2A>G	p.G2053_P2070del	Intermediate	SSCD	de novo	[7]
116	COL6A3	MA	Glycine substitution	THD	c.6158G>T	p.G2053V	UCMD	SSCD	de novo	[15]
117-1^m	COL6A3	MA	Missense	THD	c.6199G>A	p.E2067K	BM	SSCD	Dominant	[28]
117-2^m	COL6A3	MA	Missense	THD	c.6199G>A	p.E2067K	BM	Normal	Dominant	[28]
118	COL6A3	MA	Splicing	THD	c.6210+1G>A	p.G2053_P2070del	UCMD	SSCD	de novo	[25]
119	COL6A3	MA	Splicing	THD	c.6210+1G>A	p.G2053_P2070del	UCMD	SSCD	de novo	[25]
120	COL6A3	MA	Splicing	THD	c.6210+1G>A	p.G2053_P2070del	UCMD	SSCD	de novo	[25]
121	COL6A3	MA	Splicing	THD	c.6210+1G>A	p.G2053_P2070del	UCMD	SSCD	de novo	[25]
122	COL6A3	MA	Splicing	THD	c.6210+1G>A	p.G2053_P2070del	Intermediate	SSCD	de novo	[25]
123	COL6A3	MA	Splicing	THD	c.6210+1G>A	p.G2053_P2070del	UCMD	SSCD	de novo	[25]
124	COL6A3	MA	Splicing	THD	c.6210+2T>A	p.G2053_P2070del	UCMD	SSCD	de novo	[7]
125	COL6A3	MA	Glycine substitution	THD	c.6212G>A	p.G2071D	UCMD	SSCD	de novo	[8]
126	COL6A3	MA	Glycine substitution	THD	c.6247G>T	p.G2083C	Intermediate	SSCD	de novo	Novel
127	COL6A3	MA	Splicing	THD	c.6309G>A	p.G2095_K2103del	UCMD	SSCD	de novo	Novel
128	COL6A3	MA	Splicing	THD	c.6309+1G>A	p.G2095_K2103del	UCMD	SSCD	de novo	[35]
129	COL6A3	MA	Splicing	THD	c.6310-2A>G	p.G2104_D2118del	UCMD	SSCD	de novo	Novel
130	COL6A3	MA	Splicing	THD	c.6283-1G>Tⁿ c.6310-2A>Tⁿ	p.G2095_K2103delinsNSFLYLPVRLIPSL	Intermediate	SSCD	de novo	[37, 44]

IHC, immunohistochemistry; MA, mono-allelic; BA, bi-allelic; PTC, premature stop codon; THD, triple helical domain; NA, not available; UCMD, Ullrich congenital muscular dystrophy; BM, Bethlem myopathy; CD, complete deficiency; SSCD, sarcolemma-specific collagen VI deficiency
^abrothers; ^b26-2 and 26-3 are the sons of 26-1; ^d40-2 is the father of 40-1; ^e41-2 and 41-3 are the cousins of 41-1, and 41-4 and 41-5 are the sons of 41-2; ^fsisters; ^g55-2 is the son of 55-1; ^h56-2 is the daughter of 55-1; ⁱbrothers; ^j83-2 is the mother of 83-1; ^kbrothers; ^lbrothers; ^m117-2 is the mother of 117-1; ⁿtwo variants on one allele. We used the following transcripts: COL6A1, NM_001848; COL6A2, NM_001849; COL6A3, NM_004369)

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