Table 2.
COL1A1 a and COL1A2 b pathogenic variants discovered in patients with OI with intrafamilial diversity
| No. | Pathogenic variant | Gene | Mutation type | Collagen defect | Protein alteration |
|---|---|---|---|---|---|
| Pathogenic variants discovered in patients with OI with decreasing OI severity within families | |||||
| 1 | c.1821+1G>A | COL1A1 | Splice site | LOF | ‐ |
| 2 | c.750+2T>A | COL1A1 | Splice site | LOF | ‐ |
| 3 | c.858+1G>A | COL1A1 | Splice site | LOF | ‐ |
| 4 | c.1128_delT | COL1A1 | Frameshift | LOF | p.Gly377Alafs*164 |
| 5 | c.769G>A | COL1A1 | Missense | DN | p.Gly257Arg |
| 6 |
c.370‐1G>A /c.2642A>C |
COL1A1 /COL1A2 |
Splice site/Missense | LOF/DN | ./p.Glu881Ala |
| 7 | c.3305G>T | COL1A2 | Missense | DN | p.Gly1102>Val |
| 8 | c.1072G>T | COL1A2 | Missense | DN | p.Gly358Ser |
| Pathogenic variants discovered in patients with OI with progressing OI severity within families | |||||
| 1 | c.3217G>A | COL1A1 | Missense | DN | p.Gly1073Ser |
| 2 | c.2362G>A | COL1A1 | Missense | DN | p.Gly788Ser |
| 3 | c.3652G>A | COL1A1 | Missense | DN | p.Ala1218Thr |
| 4 | c.1057G>T | COL1A1 | Missense | DN | p.353G>G/C |
| 5 | c.2560G>A | COL1A1 | Missense | DN | p.Gly854Ser |
| 6 | c.2461G>A | COL1A1 | Missense | DN | p.Gly821Ser |
| 7 | c.2461G>A | COL1A1 | Missense | DN | p.Gly821Ser |
| 8 | c.2314G>A | COL1A2 | Missense | DN | p.Gly772Ser |
| 9 | c.982G>A | COL1A2 | Missense | DN | p.Gly328Ser |
| 10 | c.658C>T | COL1A1 | Nonsense | LOF | p.Arg220* |
| 11 | c.495T>A | COL1A1 | Nonsense | LOF | p.Tyr165* |
| 12 | c.1816_delG | COL1A1 | Frameshift | LOF | p.Ala606Leufs*160 |
| 13 | c.103+2T>C | COL1A1 | Splice site | LOF | ‐ |
| Pathogenic variants discovered in patients with OI without changes in OI severity within families | |||||
| 1 | c.505G>A | COL1A1 | Missense | DN | p.Glu169Lys |
| 2 | c.1A>C | COL1A1 | Missense | DN | p.Met1Leu |
| 3 | c.3223G>A | COL1A1 | Missense | DN | p.Ala1075Thr |
| 4 | c.959G>A | COL1A1 | Missense | DN | p.Gly320Asp |
| 5 | c.1102G>A | COL1A1 | Missense | DN | p.Gly368Ser |
| 6 | c.1165G>T | COL1A1 | Missense | DN | p.Gly389Cys |
| 7 | c.977G>A | COL1A1 | Missense | DN | p.Gly326Asp |
| 8 | c.2005G>A | COL1A1 | Missense | DN | p.Ala669Thr |
| 9 | c.2362G>A | COL1A1 | Missense | DN | p.Gly788Ser |
| 10 | c.2299G>A | COL1A1 | Missense | DN | p.Gly767Ser |
| 11 | c.3766G>A | COL1A1 | Missense | DN | p.Ala1256Thr |
| 12 | c.1009G>A | COL1A2 | Missense | DN | p.Gly337Ser |
| 13 | c.1009G>A | COL1A2 | Missense | DN | p.Gly337Ser |
| 14 | c.1630G>A | COL1A2 | Missense | DN | p.Gly544Ser |
| 15 | c.1009G>A | COL1A2 | Missense | DN | p.Gly337Ser |
| 16 | c.1964G>T | COL1A2 | Missense | DN | p.Gly655Val |
| 17 | c.579_delT | COL1A1 | Frameshift | LOF | p.Gly194Valfs*71 |
| 18 | c.2821_delG | COL1A1 | Frameshift | LOF | p.Gly941Valfs*167 |
| 19 | c.2393_dupC | COL1A1 | Frameshift | LOF | p.Gly800Argfs*5 |
| 20 | c.2523_delT | COL1A1 | Frameshift | LOF | p.Gly842Alafs*266 |
| 21 | c.630_delG | COL1A1 | Frameshift | LOF | p.Glu210Aspfs*3 |
| 22 | c.2523_delT, | COL1A1 | Frameshift | LOF | p.Gly842Alafs*266 |
| 23 | 2093_2110_dup | COL1A2 | Frameshift | LOF | p.Leu699_Leu704dup |
| 24 | c.1897G>T | COL1A1 | Nonsense | LOF | p.Glu633* |
| 25 | c.2089C>T | COL1A1 | Nonsense | LOF | p.Arg697* |
| 26 | c.3262G>T | COL1A1 | Nonsense | LOF | p.Gly1088* |
| 27 | c.3262G>T | COL1A1 | Nonsense | LOF | p.Gly1088* |
| 28 | c.1081C>T | COL1A1 | Nonsense | LOF | p.Arg361* |
| 29 | c.3076C>T | COL1A1 | Nonsense | LOF | p.Arg1026* |
| 30 | c.1243C>T | COL1A1 | Nonsense | LOF | p.Arg415* |
| 31 | c.3807G>A | COL1A1 | Nonsense | LOF | p.Trp1269* |
| 32 | c.2179C>T | COL1A1 | Nonsense | LOF | p.Gln727* |
| 33 | c.1821+1G>A | COL1A1 | Splice site | LOF | ‐ |
| 34 | c.1155+2T>G | COL1A1 | Splice site | LOF | ‐ |
| 35 | c.299‐1G>C | COL1A1 | Splice site | LOF | ‐ |
| 36 | c.1767+5G>A | COL1A1 | Splice site | LOF | ‐ |
| 37 | c.1354‐2A>G | COL1A1 | Splice site | LOF | ‐ |
| 38 | c.904‐9G>A | COL1A1 | Splice site | LOF | ‐ |
| 39 | c.2613+6T>C | COL1A1 | Splice site | LOF | ‐ |
| 40 | c.804+1G>A | COL1A1 | Splice site | LOF | ‐ |
| 41 | c.103+2T>C | COL1A1 | Splice site | LOF | ‐ |
| 42 | c.2614‐1G>A | COL1A1 | Splice site | LOF | ‐ |
| 43 | c.2026‐1_2031het dup | COL1A2 | Splice site | LOF | ‐ |
DN, dominant negative, LOF, loss‐of‐function; OI, osteogenesis imperfecta.
a
COL1A1 GenBank reference sequence (gDNA NG_007400.1, cDNA NM_000088.3). b COL1A2 GenBank reference sequence (gDNA NG_007405.1, cDNA NM_000089.3).
*
“Stop codon” in mutation nomenclature.