Table 1. Summary of 77 different COL2A1 mutations identified in a series of 100 affected individuals.
Patient ID | Age (years) | Score | Exon/intron | cDNA | Protein | Mutation type | Mutation effect |
---|---|---|---|---|---|---|---|
1 | 46 | 15 | del COL2A1 | del COL2A1 | Large deletion | Deletion[19] | |
2 | 54 | 13 | 02 | c.211_233dup | p.Glu79ThrfsX2 | Duplication | Frameshift |
3 | 58 | 17 | 02 | c.264_276del | p.Cys89SerfsX24 | Deletion | Frameshift |
4 | 4 | 6 | IVS 04 | c.342+1G>A | p.Asp114_Ile115insIleSerAlaAsnTyrSerHisProValLeuGlnLeuLeuX14 | RNA processing | Insertion with premature stop codon |
5 | 42 | 17 | IVS 06 | c.430-1G>C | p.Gly144ValfsX54; p.Gln125_Gly126insArgGluGlyGluAsnLeuPheLeuArgProPheLeuAlaAlaGlnValThrAspLeuX20; p.Lys143_Asn178delExon7a | RNA processing | Frameshift; insertion with premature stop codon; exon deletion |
6 | 6 | 6 | 07 | c.492delT | p.Gly165ValfsX34 | Deletion | Frameshift |
7 | 3 | 6 | 09 | c.625C>T | p.Arg209X | Nonsense | Premature stop codon |
8 | 6 | 11 | 09 | c.625C>T | p.Arg209X | Nonsense | Premature stop codon |
9 | 19 | 13 | 09 | c.625C>T | p.Arg209X | Nonsense | Premature stop codon |
10 | 12 | 14 | 09 | c.625C>T | p.Arg209X | Nonsense | Premature stop codon |
11 | 22 | 15 | 09 | c.647G>A | p.Gly216Asp | Missense | Glycine substitution |
12 | 8 | 8 | IVS 09 | c.654+1G>A | ND | RNA processing | ND |
13 | 34 | 10 | 10 | c.655G>C | p.Gly219Arg | Missense | Glycine substitution |
14 | 27 | 14 | 10 | c.665G>T | p.Gly222Val | Missense | Glycine substitution |
15 | 24 | 11 | 11 | c.744delT | p.Gly249GlufsX59 | Deletion | Frameshift |
16 | 45 | 18 | 12 | c.793delG | p.Glu265fsX43 | Deletion | Frameshift |
17 | 37 | 14 | IVS 13 | c.870+5 G> A | ND | RNA processing | ND |
18 | 30 | 9 | IVS 14 | c.925-1G>A | p.Lys308_Gly309insGluPheAlaGlyGlyGlnGluTrpGlyProArgHisX13 | RNA processing | Insertion with premature stop codon |
19 | 67 | 12 | 17 | c.1030C>T | p.Arg344X | Nonsense | Premature stop codon |
20 | 9 | 9 | 17 | c.1030C>T | p.Arg344X | Nonsense | Premature stop codon |
21 | 62 | 21 | IVS 18 | c.1123-1G>A | p.Gly375ValfsX253 | RNA processing | Frameshift |
22 | 6 | 7 | 19 | c.1172delC | p.Pro391LeufsX238 | Deletion | Frameshift |
23 | 11 | 11 | IVS 19 | c.1221+1G>A | ND | RNA processing | ND |
24 | 43 | 12 | 21 | c.1311_1313delinsCA | p.Gly438ThrfsX191 | Deletion/insertion | Frameshift |
25 | 33 | 12 | 23 | c.1428_1429insTGGC | p.Gly477TrpfsX12 | Insertion | Frameshift |
26 | 13 | 8 | 23 | c.1475G>A | p.Gly492Asp | Missense | Glycine substitution |
27 | 40 | 13 | 25 | c.1597C>T | p.Arg533X | Nonsense | Premature stop codon |
28 | 10 | 10 | 25 | c.1597C>T | p.Arg533X | Nonsense | Premature stop codon |
29 | 12 | 15 | IVS 25 | c.1680+2delGTinsAA | ND | RNA processing | ND |
30 | 24 | 10 | 26 | c.1693C>T | p.Arg565Cys | Missense | Arginine-to-cysteine substitution[20] |
31 | 20 | 8 | 26 | c.1693C>T | p.Arg565Cys | Missense | Arginine-to-cysteine substitution[20] |
32 | 9 | 7 | 26 | c.1693C>T | p.Arg565Cys | Missense | Arginine-to-cysteine substitution[20] |
33 | 11 | 19 | 27 | c.1777C>T | p.Gln593X | Nonsense | Premature stop codon |
34 | 14 | 14 | 27 | c.1828delG | p.Ala610ProfsX19 | Deletion | Frameshift |
35 | 11 | 10 | IVS 27 | c.1833+1G>A | ND | RNA processing | ND |
36 | 36 | 12 | IVS 27 | c.1833+1G>A | p.Gly609GlyfsX1 | RNA processing | Frameshift |
37 | 40 | 14 | IVS 27 | c.1833+1G>A | ND | RNA processing | ND |
38 | 17 | 17 | IVS 27 | c.1833+1 G>A | p.Gly609GlyfsX1 | RNA processing | Frameshift |
39 | 14 | 10 | IVS 28 | c.1888-2A>G | p.Gly630MetfsX53 | RNA processing | Frameshift |
40 | 13 | 6 | 29 | c.1931delC | p.Pro644LeufsX144 | Deletion | Frameshift |
41 | 40 | 19 | 30 | c.1957C>T | p.Arg653X | Nonsense | Premature stop codon |
42 | 41 | 12 | 30 | c.1957C>T | p.Arg653X | Nonsense | Premature stop codon |
43 | 4 | 6 | IVS 32 | c.2094+1G>A | ND | RNA processing | ND |
44 | 35 | 9 | IVS 32 | c.2095-1G>A | ND | RNA processing | ND |
45 | 40 | 8 | 33 | c.2101C>T | p.Arg701X | Nonsense | Premature stop codon |
46 | 31 | 10 | 33 | c.2101C>T | p.Arg701X | Nonsense | Premature stop codon |
47 | 8 | 11 | IVS 33 | c.2193+2T>C | ND | RNA processing | ND |
48 | 43 | 14 | 34 | c.2257_2264delGGCGAGAG | p.Glu754SerfsX13 | Deletion | Frameshift |
49 | 5 | 5 | 34 | c.2263_2264delAG | p.Arg755GlyfsX14 | Deletion | Frameshift |
50 | 9 | 11 | 35 | c.2353C>T | p.Arg785X | Nonsense | Premature stop codon |
51 | 14 | 10 | 35 | c.2353C>T | p.Arg785X | Nonsense | Premature stop codon |
52 | 37 | 7 | 35 | c.2353C>T | p.Arg785X | Nonsense | Premature stop codon |
53 | 33 | 8 | IVS 35 | c.2355+5G>A | ND | RNA processing | ND |
54 | 38 | 13 | IVS 35 | c2355+5G>A | p.Arg785_Gly786insValAsnGluCysGlyLeuLeuAspCysTrpAlaPheGlySerX15 | RNA processing | Insertion with premature stop codon |
55 | 11 | 11 | 36 | c.2381dupC | p.Gly795TrpfsX6 | Duplication | Frameshift |
56 | 5 | 10 | 36 | c.2382delT | p.Gly795Alafs86 | Deletion | Frameshift |
57 | 41 | 12 | 36 | c.2382delT | p.Gly795Alafs86 | Deletion | Frameshift |
58 | 14 | 9 | 38 | c.2467G>T | p.Glu823X | Nonsense | Premature stop codon |
59 | 44 | 9 | 38 | c.2493dupA | p.Pro832ThrfsX11 | Duplication | Frameshift |
60 | 66 | 13 | IVS 38 | c.2517+2T>G | ND | RNA processing | ND |
61 | 24 | 15 | IVS 38 | c.2518-1 G>A | p.Gly840ValfsX41 | RNA processing | Frameshift |
62 | 41 | 17 | 39 | c.2588-2604delCTGG TCCTCAGGGCCCC | p.Pro863LeufsX16 | Deletion | Frameshift |
63 | 39 | 17 | 40 | c.2659C>T | p.Arg887X | Nonsense | Premature stop codon |
64 | 12 | 12 | 40 | c.2673dupC | p.Ala895SerfsX49 | Duplication | Frameshift |
65 | 33 | 9 | 40 | c.2673delC | p.Pro893ArgfsX135 | Deletion | Frameshift |
66 | 9 | 14 | 41 | c.2710C>T | p.Arg904Cys | Missense | Arginine-to-cysteine substitution[20] |
67 | 18 (8 at examination) | 0 | 41 | c.2710C>T | p.Arg904Cys | Missense | Arginine-to-cysteine substitution[20] |
68 | 70 | 9 | 41 | c.2715dupT | p.Gly906TrpfsX38 | Duplication | Frameshift |
69 | 40 | 17 | 41 | c.2719dupC | p.Gly909ArgfsX35 | Duplication | Frameshift |
70 | 44 | 9 | 42 | c.2813delC | p.Pro938LeufsX90 | Deletion | Frameshift |
71 | 58 | 9 | 42 | c.2839C>T | p.Gln947X | Nonsense | Premature stop codon |
72 | 12 | 10 | 42 | c.2862C>T | p.Gly954Glyb | Synonymous | Frameshift |
73 | 11 | 8 | IVS 43 | c.3003+1G>A | ND | RNA processing | ND |
74 | 20 | 13 | IVS 43 | c.3003+5G>A | p.Gly966_Ser1001del; p.Gly990GlyfsX1a | RNA processing | Deletion; frameshift |
75 | 32 | 16 | 44 | c.3081_3087delGACGGT insCCTGG | p.Thr1028LeufsX100 | Deletion/insertion | frameshift |
76 | 18 | 17 | 44 | c.3106C>T | p.Arg1036X | Nonsense | Premature stop codon |
77 | 39 | 14 | 44 | c.3106C>T | p.Arg1036X | Nonsense | Premature stop codon |
78 | 10 | 11 | 44 | c.3106C>T | p.Arg1036X | Nonsense | Premature stop codon |
79 | 47 | 13 | 44 | c.3106C>T | p.Arg1036X | Nonsense | Premature stop codon |
80 | 45 | 10 | 44 | c.3106C>T | p.Arg1036X | Nonsense | Premature stop codon |
81 | 49 | 13 | IVS 44 | c.3111+1G>T | p.Glu1033LysfsX4 | RNA processing | Frameshift |
82 | 8 | 11 | IVS 44 | c.3112-1G>A | p.Gly1038GlufsX92 | RNA processing | Frameshift |
83 | 29 | 12 | 45 | c.3137delC | p.Pro1046LeufsX84 | Deletion | Frameshift |
84 | 8 | 12 | 45 | c.3137dupC | p.Gly1047TrpfsX11 | Duplication | Frameshift |
85 | 17 | 13 | 45 | c.3138delT | p.Gly1047AlafsX83 | Deletion | Frameshift |
86 | 20 | 12 | 46 | c.3228delT | p.Gly1077AlafsX53 | Deletion | Frameshift |
87 | 35 | 18 | 46 | c.3258_3261delAGAC | p.Asp1087GlufsX42 | Deletion | Frameshift |
88 | 42 | 9 | 47 | c.3325delC | p.Gln1109ArgfsX21 | Deletion | Frameshift |
89 | 18 | 11 | 48 | c.3392G>C | p.Gly1131Ala | Missense | Glycine substitution |
90 | 8 | 11 | 50 | c.3574C>T | p.Arg1192X | Nonsense | Premature stop codon |
91 | 47 | 16 | 50 | c.3574C>T | p.Arg1192X | Nonsense | Premature stop codon |
92 | 40 | 18 | 50 | c.3574C>T | p.Arg1192X | Nonsense | Premature stop codon |
93 | 42 | 11 | 51 | c.3623delC | p.Pro1208LeufsX19 | Deletion | Frameshift |
94 | 33 | 12 | 51 | c.3641dupC | p.Gly1215TrpfsX38 | Duplication | Frameshift |
95 | 41 | 10 | 51 | c.3864-3865delCT | p.Cys1289ProfsX3 | Deletion | Frameshift |
96 | 11 | 10 | 51 | c.3878G>A | p.Trp1293X | Nonsense | Premature stop codon |
97 | 55 | 12 | 52 | c.3891_3898dupCTACTGGA | p.Ile1300ThrfsX15 | Duplication | Frameshift |
98 | 53 | 12 | 52 | c.3903delC | p.Asn1303ThrfsX9 | Deletion | Frameshift |
99 | 52 | 17 | IVS 52 | c.4074+1 G>T | p.Gln1238_Leu1411del; p.Trp1348CysfsX17a | RNA processing | Deletion; frameshift |
100 | 8 | 10 | IVS 53 | c.4317+2T>C | ND | RNA processing | ND |
Indication N-propeptide (p.26–181) – triple helical domain (p.201–1214) – C-propeptide (p.1242–1487) |
IVS, intervening sequence; ND, not determined.
Items in italics represent recurrent mutations.
Exons are numbered 1–54.
cDNA mutations are numbered starting from the first base of the start codon (ATG) of the cDNA reference sequence (GenBank accession number NM_001844).
Amino-acid mutations were numbered from the first Methionine of the α1(II) collagen chain (GenBank L10347).
Score as calculated by the proposed scoring system in Table 2.
Splice site mutations with multiple isoforms: see Supplementary Figure 1.
Synonymous mutation: see Supplementary Figure 2.