Putative disease variants of Mendelian ALS genes
| Gene | Variant | SIFT | PolyPhen | Model | fALS | sALS | IRL | EUR | GLO |
|---|---|---|---|---|---|---|---|---|---|
| ALS2* | c.3094C>T(p.[Arg1032Cys]) | Deleterious | Probably damaging | D | 0/49 | 1/375 | 0/274 | NR | NR |
| ALS2* | c.2606A>C(p.[Gln869Pro]) | Deleterious | Probably damaging | D | 0/50 | 1/390 | 0/290 | NR | NR |
| ALS2* | c.2566A>G(p.[Thr856Ala]) | Tolerated | Possibly damaging | D | 0/47 | 1/373 | 0/253 | NR | NR |
| ALS2* | c.2408A>G(p.[Lys803Arg]) | Tolerated | Possibly damaging | D | 0/50 | 1/391 | 0/289 | NR | NR |
| ALS2* | c.2098A>G(p.[Thr700Ala]) | Tolerated | Benign | D | 0/50 | 2/386 | 0/279 | NR | NR |
| C9orf72 | Repeat expansion | – | – | D | 15/45 | 24/367 | 0/188 | NR | NR |
| FUS | c.1574C>T(p.[Pro525Leu]) | Deleterious | Possibly damaging | D | 0/43 | 2/319 | 0/250 | NR | NR |
| OPTN | c.1192C>G(p.[Gln398Glu]) | Tolerated | Benign | D | 0/50 | 1/368 | 0/243 | NR | NR |
| SETX | c.7682C>T(p.[Ser2561Leu]) | Tolerated | Benign | D | 0/50 | 2/358 | 0/253 | 1/4553 | 1/6756 |
| SETX | c.7645G>A(p.[Val2549Ile]) | Deleterious | Benign | D | 0/50 | 2/389 | 0/305 | 0/4605 | 1/6808 |
| SETX | c.5842A>G(p.[Met1948Val]) | Deleterious | Probably damaging | D | 0/50 | 1/388 | 0/279 | NR | NR |
| SETX | c.5587A>G(p.[Thr1863Ala]) | Deleterious | Probably damaging | D | 1/50 | 0/391 | 0/278 | NR | NR |
| SETX | c.2975A>G(p.[Lys992Arg]) | Deleterious | Benign | R | 1/50 | 0/388 | 0/280 | NR | NR |
| SETX | c.2842C>A(p.[Pro948Thr]) | Tolerated | Benign | D | 1/50 | 0/387 | 0/282 | NR | NR |
| SETX | c.2755G>C(p.[Val919Leu]) | Tolerated | Benign | D | 0/50 | 1/384 | 0/266 | NR | NR |
| SETX | c.814C>G(p.[His272Asp]) | Deleterious | Probably damaging | D | 0/50 | 1/387 | 0/280 | NR | NR |
| TARDBP | c.859G>A(p.[Gly287Ser]) | Tolerated | Benign | D | 0/50 | 2/390 | 0/300 | NR | NR |
| VCP | c.2249A>G(p.[Asn750Ser]) | Tolerated | Benign | D | 0/50 | 1/389 | 0/306 | NR | NR |
Variants previously associated with ALS are shown in bold.
*Gene conventionally associated with recessively inherited ALS.
D—Variant may cause disease in a dominant fashion and carrier frequencies relate to heterozygote carriers.
R—Variants may cause disease in a recessive fashion and carrier frequencies relate to homozygous carriers.
NR—Variant not reported within either the 1000 genomes or ESP6500 datasets (samples of European ancestry=4679, total number of samples=7595).
ALS2—ENST00000264276; FUS—ENST00000254108; OPTN—ENST00000263036; SETX—ENST00000224140; TARDBP—ENST00000240185; VCP—ENST00000358901.
ALS, amyotrophic lateral sclerosis; ESP, Exome Sequencing Project.