List of VWF variants with discrepant classification in the literature
| Variant . | N of patients . | VWF activity/ VWF:Ag ratio . | VWF:CB/ VWF:Ag ratio . | VWD diagnosis* . | VWD type in literature . |
|---|---|---|---|---|---|
| p.Tyr1107Cys | 1 | 0.63 | 0.9 | 2A(IIE) | 2A(IIE)8,27 or type 147 |
| p.Cys1130Phe | 2 | 0.65 (0.56-0.75) | 0.27 (0.2-0.35) | 2A(IIE) | 2A(IIE)27,46 or type 149,53 |
| p.Tyr1146Cys | 1 | 0.62 | 0.25 | 2A(IIE) | 2A(IIE)9,27,54 or type 154,46,55 |
| p.Arg924Gln-p.Arg1315Leu† | 7 | 0.45 (0.24-0.68) | 0.57 (0.38-0.95) | 2M/2A | 2A,28,54 2M,48 2A(IIE),56 or type 154 |
| p.Arg1315Cys | 3 | 0.4 (0.32-0.51) | 0.8 (0.53-0.93) | 2M | 2A,38,39,54 2M,8,27,47,54 type 18,38,47,51,54 or 2A/2M28 |
| p.Arg1374His | 24 | 0.25 (0.16-0.54) | 0.51 (0.19-0.85) | 2M/2A | 2A,28,29,53,54 2M,27,41,46,54 or 1C38 |
| p.Arg1374Cys | 6 | 0.34 (0.15-0.66) | 0.57 (0.1-0.61) | 2M/2A | 2A,38,54 2M,27,41,53,57 1C,38 or 2A/2M28 |
| p.Arg1399Cys | 3 | 0.33 (0.29-0.52) | 0.86 (0.62-1.1) | 2M | 2M8,45,46 or 2U47 |
| p.Ala1716Phe | 15 | 0.84 (0.5-1.1) | 0.63 (0.37-1) | 2M(CB) | 2M(CB)27 or type 143 |
| p.Val1820Glu | 2 | 0.8 (0.77-0.83) | 0.31 (0.3-0.33) | 2M(CB) | 2M(CB)44 or type 144 |
| Variant . | N of patients . | VWF activity/ VWF:Ag ratio . | VWF:CB/ VWF:Ag ratio . | VWD diagnosis* . | VWD type in literature . |
|---|---|---|---|---|---|
| p.Tyr1107Cys | 1 | 0.63 | 0.9 | 2A(IIE) | 2A(IIE)8,27 or type 147 |
| p.Cys1130Phe | 2 | 0.65 (0.56-0.75) | 0.27 (0.2-0.35) | 2A(IIE) | 2A(IIE)27,46 or type 149,53 |
| p.Tyr1146Cys | 1 | 0.62 | 0.25 | 2A(IIE) | 2A(IIE)9,27,54 or type 154,46,55 |
| p.Arg924Gln-p.Arg1315Leu† | 7 | 0.45 (0.24-0.68) | 0.57 (0.38-0.95) | 2M/2A | 2A,28,54 2M,48 2A(IIE),56 or type 154 |
| p.Arg1315Cys | 3 | 0.4 (0.32-0.51) | 0.8 (0.53-0.93) | 2M | 2A,38,39,54 2M,8,27,47,54 type 18,38,47,51,54 or 2A/2M28 |
| p.Arg1374His | 24 | 0.25 (0.16-0.54) | 0.51 (0.19-0.85) | 2M/2A | 2A,28,29,53,54 2M,27,41,46,54 or 1C38 |
| p.Arg1374Cys | 6 | 0.34 (0.15-0.66) | 0.57 (0.1-0.61) | 2M/2A | 2A,38,54 2M,27,41,53,57 1C,38 or 2A/2M28 |
| p.Arg1399Cys | 3 | 0.33 (0.29-0.52) | 0.86 (0.62-1.1) | 2M | 2M8,45,46 or 2U47 |
| p.Ala1716Phe | 15 | 0.84 (0.5-1.1) | 0.63 (0.37-1) | 2M(CB) | 2M(CB)27 or type 143 |
| p.Val1820Glu | 2 | 0.8 (0.77-0.83) | 0.31 (0.3-0.33) | 2M(CB) | 2M(CB)44 or type 144 |
If the number of patients was more than one, the median (range) of values was used.
The final diagnosis of patients was established considering both ratios of VWF activity/VWF:Ag and VWF:CB/VWF:Ag as well as the VWF multimer profile. Type 2A(IIE) showed an aberrant subband structure in multimer pattern, with a lack of the satellite bands but pronounced inner bands of the triplet. Type 2M/2A patients had decreased VWF activity/VWF:Ag and VWF:CB/VWF:Ag ratios, more pronounced in the former, and they had slight loss of large VWF multimers (supplemental Figures 1-3). Type 2M had a reduced VWF activity/VWF:Ag ratio, with a normal VWF:CB/VWF:Ag ratio; however, in type 2MCB, the opposite was observed.
All the cited references reported p.Arg1315Leu alone, except Michiels et al,56 in which p.Arg1315Leu was found in cis position with the p.Arg924Gln variant, the same as in our study.