TABLE 1.
Classification of families
| Family number | No. of carriers | Familial phenotype | COL3A1 variant (NM_000090.4) | Predicted consequence | Variant type | ACMG Classification |
|---|---|---|---|---|---|---|
| 1 | 1 | Severe | Complete deletion | — | Null | Pathogenic (PVS1, PM2, PP3, PP4) |
| 2 | 4 | Unclassified | c.202dupG | p.Asp68Glyfs*33 | Null | Pathogenic (PVS1, PM2, PP1) |
| 3 | 4 | Unclassified | c.413delC | p.Pro138Leufs*27 | Null | Pathogenic (PVS1, PM2, PP1) |
| 4 | 1 | Unclassified | c.636 + 4A > T |
Reduced strength of splice donor site at exon 7 (MaxEntScan score 9.1 > 5.0) |
Splice site | Pathogenic (PS3, PM2, PP4, PP5) |
| 5 | 3 | Severe | c.970G > A | p.Gly324Ser | Missense | Pathogenic (PM1, PM2, PP1, PP2, PP3, PP4) |
| 6 | 13 | Attenuated | c.989G > A | p.Gly330Asp | Missense | Pathogenic (PM1, PM2, PP1, PP2, PP3) |
| 7 | 1 | Unclassified | c.1223G > A | p.Gly408Glu | Missense | Pathogenic (PM1, PM2, PM5, PP2, PP3, PP5) |
| 8 | 3 | Attenuated | c.1455 + 5G > A | Reduced strength of splice donor site at exon 20 (MaxEntScan score 9.2 > 3.8) | Splice site | Pathogenic (PS3, PM2, PM4, PP1, PP3) |
| 9 | 2 | Unclassified | c.1573G > A | p.Gly525Ser | Missense | Likely Pathogenic (PM1, PM2, PP1, PP2, PP3) |
| 10 | 1 | Unclassified | c.1662 + 5G > A | Reduced strength of splice donor site at exon 23 (MaxEntScan score 5.5 > −) | Splice site | Pathogenic (PS2, PS3, PM2, PM4, PM6) |
| 11 | 10 | Attenuated | c.1691G > A | p.Gly564Asp | Missense | Pathogenic (PM1, PM2, PM5, PP1, PP2, PP3) |
| 12 | 1 | Severe | c.1923 + 1G > A | Reduced strength of splice donor site at exon 27 (MaxEntScan score 7.6 > −) | Splice site | Pathogenic (PVS1, PM2, PP5) |
| 13 | 3 | Unclassified | c.2283 + 1G > A | Reduced strength of splice donor site at exon 32 (MaxEntScan score 9.3 > −) | Splice site | Pathogenic (PVS1, PM2, PP5) |
| 14 | 4 | Unclassified | c.2510G > A | p.Gly192Ser | Missense | Pathogenic (PM1, PM2, PP1, PP2, PP3, PP5) |
| 15 | 5 | Unclassified | c.2689G > A | p.Gly897Ser | Missense | Pathogenic (PM1, PM2, PM5, PP1, PP5, PP2, PP3) |
| 16 | 1 | Severe | c.2915G > A | p.Gly972Asp | Missense | Pathogenic (PM1, PM2, PM5, PP5, PP2, PP3) |
| 17 | 1 | Severe | c.3039 + 2 T > G | Reduced strength of splice donor site at exon 41 (MaxEntScan score 7.8 > −) | Splice site | Pathogenic (PVS1, PM2, PP3) |
| 18 | 13 | Attenuated | c.3256‐1G > A | Introduction of novel splice acceptor site 1 bp inside exon 45 (MaxEntScan score 5.0) | Splice site | Pathogenic (PVS1, PM2, PP1, PP5) |
| 19 | 2 | Unclassified | c.3302G > T | p.Gly1101Val | Missense | Pathogenic (PM1, PM2, PM5, PP1, PP2, PP3, PP5) |
| 20 | 6 | Attenuated | c.3325C > T | p.Arg1109* | Null | Pathogenic (PVS1, PM2, PP1, PP5,) |
| 21 | 1 | Severe | c.3418‐2A > C | Reduced strength of splice acceptor site at exon 47 (MaxEntScan score 6.2 > −) | Splice site | Pathogenic (PVS1, PS2, PM2, PM6) |
| 22 | 1 | Severe | c.3418G > A |
p.Gly1140Arg Reduced strength of splice acceptor site at exon 47 (MaxEntScan score 6.2 > 4.9) |
Missense | Pathogenic (PS3, PM1, PM2, PP3, PM5, PP2) |
| 23 | 1 | Unclassified | c.3490G > T | p.Gly1164Trp | Missense | Pathogenic (PS3, PM1, PM2, PM5, PM6, PP2, PP3, PP5) |
| 24 | 1 | Unclassified | c.3490G > A | p.Gly1164Arg | Missense | Pathogenic (PS1, PM1, PM2, PM5, PP2, PP3, PP5) |
| 25 | 4 | Severe | c.3509G > A | p.Gly1170Asp | Missense | Pathogenic (PM1, PM2, PM5, PP1, PP2, PP3, PP5) |