Table 2. Type 1 von Willebrand disease mutations/neutral variants identified among the 126 index cases.
SNP ID | Chr. position a | Base change | Exon | Amino acid change | Index cases | MAF in ExAC b | In silico prediction c | VWD type in database d |
---|---|---|---|---|---|---|---|---|
Nonsense | ||||||||
rs61750595 | 6127609 | c.4975C > T | 28 | p.R1659* | 4 | 0.00008 | – | 3 |
New | 6094247 | c.6940C > T | 40 | p.Q2314* | 1 | 0 | – | |
rs61751296 | 6078503 | c.7603C > T | 45 | p.R2535* | 3 | 0.00005 | – | 3 |
New | 6058958 | c.8247C > A | 51 | p.Y2749* | 1 | 0 | – | |
Missense | ||||||||
New | 6204703 | c.580A > G | 6 | p.S194G | 1 | 0 | 1 | |
rs199570108 | 6181528 | c.1078G > A | 9 | p.G360S | 1 | 0.0002 | 4 | |
rs41276738 | 6143978 | c.2561G > A | 20 | p.R854Q | 2 | 0.004 | 3 | 1 |
rs267607328 | 6131977 | c.3467C > T | 26 | p.T1156M | 1 | 0 | 4 | 1 |
rs61749367 | 6128898 | c.3686T > G | 28 | p.V1229G | 2 | 0.001 | 0 | 1 |
rs61749368 | 6128892 | c.3692A > C | 28 | p.N1231T | 2 | 0.001 | 1 | 1 |
rs61750074 | 6128449 | c.4135C > T | 28 | p.R1379C | 1 | 0.00002 | 3 | 1 |
rs61750079 | 6128346 | c.4238C > T | 28 | p.P1413L | 1 | 0.00001 | 4 | 1 |
rs1800386 | 6127833 | c.4751A > G | 28 | p.Y1584C | 11 | 0.004 | 3 | 1 |
rs61750604 | 6125715 | c.5278G > A | 30 | p.V1760I | 1 | 0.001 | 0 | 1 |
New | 6122758 | c.5509C > T | 32 | p.R1837W | 1 | 0 | 4 | |
New | 6121281 | c.5636G > T | 33 | p.C1879F | 1 | 0 | 3 | |
New | 6121256 | c.5661G > T | 33 | p.K1887N | 1 | 0 | 1 | |
New | 6120827 | c.5798C > T | 34 | p.P1933L | 1 | 0 | 3 | |
rs144072210 | 6105380 | c.5851A > G | 35 | p.T1951A | 1 | 0.001 | 1 | |
New | 6103210 | c.6416G > A | 37 | p.C2139Y | 1 | 0 | 4 | |
New | 6094737 | c.6893C > T | 39 | p.T2298M | 1 | 0.0002 | 3 | |
rs764980510 | 6092417 | c.6980G > A | 41 | p.C2327Y | 4 | 0.00003 | 4 | |
rs144769404 | 6092390 | c.7007C > T | 41 | p.P2336L | 1 | 0.0002 | 0 | |
New | 6090995 | c.7244C > T | 42 | p.T2415I | 1 | 0 | 3 | |
New | 6085371 | c.7343G > A | 43 | p.C2448Y | 1 | 0 | 4 | |
rs61751286 | 6085324 | c.7390C > T | 43 | p.R2464C | 1 | 0.00006 | 3 | 1 |
rs61751289 | 6085284 | c.7430G > A | 43 | p.C2477Y | 1 | 0 | 4 | 1 |
New | 6078427 | c.7679G > T | 45 | p.G2560V | 1 | 0 | 4 | |
rs61751302 | 6062708 | c.7940C > T | 48 | p.T2647M | 1 | 0.003 | 1 | 1 |
Synonymous and splice | ||||||||
rs2229444 | 6219682 | c.390C > T | 5 | SYN | 3 | 0.003 | 1 | |
rs143054357 | 6204737 | c.546G > A | 6 | SYN | 1 | 0.001 | 2 | |
New | 6173411 | c.1432 + 1G > T | 12 | Splice | 1 | 0 | 2 | |
New | 6128504 | c.4080C > T | 28 | SYN | 1 | 0 | 2 | |
rs140464171 | 6128438 | c.4146G > T | 28 | SYN | 2 | 0.0009 | 2 | Polym. |
New | 6128162 | c.4422A > G | 28 | SYN | 1 | 0 | 1 | |
rs144796763 | 6128141 | c.4443G > T | 28 | SYN | 1 | 0.002 | 1 | |
rs55784921 | 6103738 | c.6099C > T | 36 | SYN | 2 | 0.002 | 1 | Polym. |
rs55944252 | 6085370 | c.7344C > T | 43 | SYN | 1 | 0.0003 | 2 | Polym. |
rs41276732 | 6061593 | c.8079C > T | 49 | SYN | 3 | 0.003 | 2 | |
Deletion/duplication | ||||||||
New | Deletion | 14–52 | – | 1 | – | – | ||
New | 6166017 | c.1931_1945 e | 15 | – | 1 | – | – | |
New | 6128169 | c.4414delG | 28 | p.D1472Tfs*53 | 1 | 0 | – | |
New | Deletion | 28 | – | 1 | – | – | ||
New | Deletion | 28 | – | 1 | – | – |
Abbreviations: Chr., chromosome; ExAC, Exome Aggregation Consortium; MAF, minor allele frequency; SNP, single nucleotide polymorphism; VWD, von Willebrand disease.
According to GRCh37p13.
MAF observed in 33,000 individuals from the non-Finnish European population in the ExAC database.
For missense mutations, the predictions are classified according to damaging (1) or tolerated (0) using the programs SIFT, PolyPhen-2, Condel 2.0, and MutationTaster. Synonymous changes are classified as potential alteration of splicing (1) or not (0) using Human Splicing Finder and NNSPLICE. The table presents the sum of all predictions.
von Willebrand factor Variant Database, previously ISTH-SSC VWF Online Database.
Complete base change is c.1931_1945 + 5delAGCCAGGCCGCTGTGGTGCG.