Table 1:
Frameshift (A), nonsense (B) and missense (C) ARMC5 mutations identified in PBMAH patients. N/A: Not Available. The location of variants has been described on the transcript ENST00000268314.8/NM00115247. DANN score is a scoring methology ranging from 0 to 1 with 1 being the most pathogenic [31]. The allele frequence is based on the gnomAD exosomes.
| A. | cDNA | Protein | Domain | Allele | Number of index PBMAH cases | References |
|---|---|---|---|---|---|---|
| c.164_165insG | p.A55fs | - | Somatic | 1 | Elbelt et al., 2014 | |
| - | p.G57Efs*80 | - | Germline | 1 | Assie et al., 2013; Espiard et al., 2015 | |
| - | p.G57Gfs*45 | - | Germline | 1 | Gagliardi et al., 2014 | |
| - | p.I58Nfs*45 | - | Germline | 1 | Alencar et al., 2014 | |
| c.174dupC | p.E59Rfs*44 | - | Germline | 1 | Albiger et al., 2016 | |
| c.194delG | p.G65Afs*72 | - | Germline | 1 | Albiger et al., 2016 | |
| - | p.A72Lfs*36 | - | Somatic | 1 | Assie et al., 2013; Espiard et al., 2015 | |
| c.220_222delinsTT | p.L74Ffs*63 | - | Germline | 1 | Albiger et al., 2016 | |
| - | p.A80G(;)S82Vfs*5 | - | Somatic | 1 | Espiard et al., 2015 | |
| - | p.A83Rfs*51 | - | Somatic | 1 | Alencar et al., 2014 | |
| - | p.P93Rfs*40 | - | Somatic | 1 | Assie et al., 2013; Espiard et al., 2015 | |
| - | p.A97Gfs*4 | - | Somatic | 1 | Alencar et al., 2014 | |
| c.305_341del | p.S102fs | - | Somatic | 1 | Elbelt et al., 2014 | |
| c.311delC | p.A104fs | - | Somatic | 1 | Elbelt et al., 2014 | |
| - | p.A104Gfs*7 | - | Germline | 2 | Assie et al., 2013; Espiard et al., 2015 | |
| c.315_316insG | p.A106fs | - | Somatic | 1 | Elbelt et al., 2014 | |
| - | p.A106Rfs*31 | - | Germline | 1 | Espiard et al., 2015 | |
| - | p.S107Gfs*8 | - | Somatic | 1 | Assie et al., 2013 | |
| c.325_326delinsT | p.P109Sfs*28 | - | Somatic | 1 | Albiger et al., 2016 | |
| c.323_324insC | p.A110fs*9 | - | Germline | 2 | Elbelt et al., 2014; Bourdeau et al., 2016 | |
| c.327delC | p.A110Pfs*27 | - | Somatic | 2 | Assie et al., 2013; Espiard et al., 2015; Correa et al., 2015 | |
| c.346delT | p.S116Rfs*21 | - | Somatic | 1 | Correa et al., 2015 | |
| c.456–475+5del28 | Armadillo | Somatic | 1 | Assie et al., 2013 | ||
| c.608delG | p.S203Tfs*2 | Armadillo | Somatic | 1 | Correa et al., 2015 | |
| - | p.A206Dfs*22 | Armadillo | Somatic | 1 | Assie et al., 2013; Espiard et al., 2015 | |
| - | p.L220Sfs*35 | Armadillo | Somatic | 1 | Espiard et al., 2015 | |
| c.789_808del20 | p.E264Pfs*5 | Armadillo | Somatic | 1 | Correa et al., 2015 | |
| - | p.A296Cfs*34 | Armadillo | Germline | 1 | Assie et al., 2013; Espiard et al., 2015 | |
| c.1042delC | p.L348Wfs*27 | Armadillo | Somatic | 1 | Albiger et al., 2016 | |
| c.1330delA | p.T444Pfs*16 | Armadillo | Germline | 1 | Gagliardi et al., 2014 | |
| - | p.A492Pfs*52 | - | Somatic | 1 | Assie et al., 2013; Espiard et al., 2015 | |
| c.1506_1507delCA | p.R502fs | - | Somatic | 1 | Elbelt et al., 2014 | |
| c.1735–1738delTGCC | p.C579Sfs*49 | - | Germline | 1 | Faucz et al., 2014 | |
| - | p.V584Afs*19 | - | Somatic | 1 | Assie et al., 2013; Espiard et al., 2015 | |
| - | p.A702_S706del | - | Germline | 1 | Assie et al., 2013; Espiard et al., 2015 | |
| - | p.F700del | - | N/A | 1 | Assie et al., 2013; Espiard et al., 2015 | |
| - | p.L705Ffs*12 | - | Somatic | 1 | Espiard et al., 2015 | |
| - | p.L708Pfs*9 | - | Somatic | 1 | Espiard et al., 2015 | |
| c.2139delT | p.T715Lfs*1 | - | Germline | 1 | Gagliardi et al., 2014 | |
| c.2444delG | p.A815Lfs*102 | BTB | Somatic | 1 | Correa et al., 2015 |
| B. | cDNA | Protein | Domain | SNP | Allele | Number of index PBMAH cases | References |
|---|---|---|---|---|---|---|---|
| c.−117 A>C | - | - | rs76210462 | Germline | 1 | Albiger et al., 2016 | |
| c.91A>T | p.K31X | - | - | N/A | 1 | Assie et al., 2013; Espiard et al., 2015 | |
| c.118_120delCTGinsTGA | p.L40X | - | - | Somatic | 1 | Assie et al., 2013; Espiard et al., 2015 | |
| c.226 C>T | p.R76X | - | rs1340161811 | Somatic | 1 | Assie et al., 2013; Espiard et al., 2015 | |
| c.256 C>T | p.Q86X | - | rs587777660 | Germline | 1 | Assie et al., 2013; Espiard et al., 2015 | |
| c.453–475+5del28 | - | - | - | Somatic | 1 | Espiard et al., 2015 | |
| c.517C>T | p.R173X | - | - | Germline | 2 | Berthon et al., 2019; Liu et al., 2018 | |
| c.703C>T | p.Q235X | - | - | Somatic | 2 | Espiard et al., 2015; Berthon et al., 2019 | |
| c.799C>T | p.R267X | Armadillo | rs369721476 | Germline | 4 | Assie et al., 2013; Espiard et al., 2015 | |
| c.807C>A | p.C269X | Armadillo | - | Somatic | 1 | Correa et al., 2015 | |
| c.1033 C>T | p.Q345X | Armadillo | - | Somatic | 1 | Correa et al., 2015 | |
| c.1059 C>A | p.C353X | Armadillo | - | Somatic | 1 | Correa et al., 2015 | |
| c.1090 C>T | p.R364X | Armadillo | rs1386368908 | Germline | 3 | Albiger et al., 2016; Faucz et al., 2014 | |
| c.1158 G>A | p.W386X | Armadillo | - | Germline | 1 | Alencar et al., 2014 | |
| c.1288 G>T | p.E430X | - | - | N/A | 1 | Assie et al., 2013; Espiard et al., 2015 | |
| c.1297 G>T | p.E433X | - | - | Somatic | 1 | Elbelt et al., 2014 | |
| c.1428 G>A | p.W476X | - | - | Germline | 1 | Correa et al., 2015 | |
| c.1712C>G | p.S571X | - | - | Somatic | 1 | Berthon et al., 2019 | |
| c.1855 C>T | p.R619X | - | rs766717248 | Germline/Somatic | 1 | Assie et al., 2013; Espiard et al., 2015 | |
| c.1960 C>T | p.R654X | - | rs1379678857 | Somatic | 1 | Elbelt et al., 2014 | |
| c.2029 G>T | p.E677X | - | - | Somatic | 1 | Bourdeau et al., 2016 | |
| c.2290 C>T | p.R764X | BTB | rs778422149 | Germline | 3 | Albiger et al., 2016; Espiard et al., 2015 | |
| c.2336 C>G | p.S779X | BTB | - | Germline | 1 | Alencar et al., 2014 |
| C. | cDNA | Protein | Domain | SNP | Allele | Prediction | DANN score | Results of in vitro testing | Number of index PBMAH cases | Allele frequency | References |
|---|---|---|---|---|---|---|---|---|---|---|---|
| c.*234_*238dup | - | 3’UTR | rs142544346 | Germline | - | - | - | 1 | 0.03943 | Albiger et al., 2016 | |
| c.41 T>A | p.F14Y | - | rs151069962 | Germline | Missense | 0.9271 | - | 2 | 0.048 | Faucz et al., 2014 | |
| c.167 G>C | p.G56A | - | rs780112907 | Germline | Missense | 0.9586 | - | 1 | 0 | Albiger et al., 2016 | |
| c.247G>C | p.A83P | - | - | Somatic | Missense | 0.9852 | - | 1 | - | Correa et al., 2015 | |
| c.343 T>C | p.S115P | - | rs199693319 | Germline | Missense | 0.3845 | - | 1 | 0.0007388 | Faucz et al., 2014 | |
| c.415T>C | p.C139R | - | - | Somatic | Missense | - | Pathogenic | 1 | - | Assie et al., 2013; Espiard et al., 2015 | |
| c.446 C>T | p.L156F | Armadillo | rs114930262 | Germline | Missense | 0.9934 | - | 1 | 0.001592 | Faucz et al., 2014 | |
| c.476–1G>A | - | Armadillo | - | Somatic | Splice site | 0.9945 | - | 1 | - | Correa et al., 2015 | |
| c.508 A>G | p.I170V | Armadillo | rs35923277 | Germline | Missense | 0.9981 | - | 6 | 0.03638 | Faucz et al., 2014 | |
| c.943 C>T | p.R315W | Armadillo | Somatic/Germline | Missense | 0.9989 | Pathogenic | 2 | 4.096E-06 | Assie et al., 2013; Espiard et al., 2015; Gagliardi et al., 2014 | ||
| c.944 G>A | p.R315Q | Armadillo | rs1415974570 | Germline | Missense | 0.9994 | - | 1 | 4.096E-06 | Faucz et al., 2014 | |
| c.952C>G | p.L318V | Armadillo | rs1293014259 | Germline | Missense | 0.9929 | - | 1 | 8.198E-06 | Alencar et al., 2014 | |
| c.992T>C | p.L331P | Armadillo | - | Somatic | Missense | 0.9978 | Pathogenic | 1 | - | Assie et al., 2013; Espiard et al., 2015 | |
| c.1084 C>T | p.R362W | Armadillo | rs1385397608 | Germline/Somatic | Missense | 0.9992 | - | 2 | 0.00003232 | Albiger et al., 2016; Elbelt et al., 2014 | |
| c.1085G>T | p.R362L | Armadillo | - | Somatic | Missense | 0.9985 | Pathogenic | 1 | - | Assie et al., 2013; Espiard et al., 2015 | |
| c.1094T>C | p.L365P | Armadillo | rs587777663 | Germline | Missense | 0.9987 | - | 1 | - | Alencar et al., 2014 | |
| c.1181T>C | p.L394P | Armadillo | - | Germline | Missense | 0.9989 | - | 1 | - | Alencar et al., 2014 | |
| c.1448 C>T | p.P483L | - | rs552657393 | Germline | Missense | 0.6814 | - | 1 | 0.00003085 | Albiger et al., 2016 | |
| c.1643T>C | p.L548P | - | rs587777661 | Germline | Missense | 0.9973 | Pathogenic | 1 | - | Assie et al., 2013; Espiard et al., 2015 | |
| c.1739 T>C | p.L580P | - | - | Germline | Missense | 0.9989 | - | 1 | - | Albiger et al., 2016 | |
| c.1751T>A | p.V584E | - | - | Somatic | Missense | 0.9909 | - | 1 | - | Correa et al., 2015 | |
| c.1777 C>T | p.R593W | - | rs587777662 | Germline | Missense | 0.9989 | - | 2 | 0.00003236 | Faucz et al., 2014; Gagliardi et al., 2014 | |
| c.1969T>C | p.C657R | - | - | Germline | Missense | 0.9972 | Pathogenic | 1 | - | Assie et al., 2013; Espiard et al., 2015 | |
| c.1971C>G | p.C657W | - | - | Somatic | Missense | 0.9711 | - | 1 | - | Alencar et al., 2014 | |
| c.1975 C>T 1 | p.R659C | - | rs759844590 | Germline | Missense | 0.2974 | - | 1 | 4.079E-06 | Albiger et al., 2016 | |
| c.1991T>G | p.I664S | - | - | Germline | Missense | 0.9947 | Pathogenic | 1 | - | Espiard et al., 2015 | |
| c.2114 C>T 2 | p.A705V | - | rs11150624 | Germline | Missense | 0.3192 | - | 1 | 0.3375 | Bourdeau et al., 2016 | |
| c.2192 C>G | p.P731R | - | rs200951744 | Germline | Missense | 0.9943 | - | 1 | 0.001357 | Albiger et al., 2016 | |
| c.2207A>C | p.Y736S | - | - | Somatic | Missense | 0.9922 | Pathogenic | 1 | - | Assie et al., 2013; Espiard et al., 2015 | |
| c.2228C>T | p.A743V | BTB | - | Somatic | Missense | 0.9974 | - | 1 | - | Correa et al., 2015 | |
| c.2261T>C | p.L754P | BTB | - | Germline | Missense | 0.9991 | Pathogenic | 1 | - | Espiard et al., 2015 | |
| c.2393 G>C | p.G798A | BTB | rs115611533 | Germline | Missense | 0.2099 | - | 2 | 0.008979 | Faucz et al., 2014 | |
| c.2405C>G | p.P802R | BTB | - | Somatic | Missense | 0.9982 | - | 1 | - | Correa et al., 2015 | |
| c.2423A>C | p.H808P | BTB | - | Germline | Missense | 0.9857 | - | 1 | - | Alencar et al., 2014 | |
| c.2692C>T | p.R898W | - | rs587777659 | Germline | Missense | 0.9992 | Pathogenic | 4 | 9.825E-06 | Assie et al., 2013; Espiard et al., 2015; Faucz et al., 2014 |
1, 2
Variants located on the transcript ENST00000457010.6/NM_024742; the equivalent on the transcript NM_001105247c.1864+111C>G and c.1864+250C>T, respectively.