Table 4.
Pathogenic and likely pathogenic variants in ALS genes (Classes 4 and 5).
| Gene | Class | Variant DNA |
Variant Protein |
MAF % * | dbSNP | Additional Variants | Clinical Notes | Patient | Ref. |
|---|---|---|---|---|---|---|---|---|---|
| OPTN | 5 | c.941A>T | p.Gln314Leu | 0%-0.02%-0.01% | rs142812715 | (AR) ALS2: c.331G>A (p.Val111Ile) het [rs61745503, MAF *: 0.04%-0.02%-0.03%] (Class3) | Bulbar-Spinal ALS laboratory supported | P087 | [22,23] |
| OPTN | 5 | c.1442C>T | p.Ala481Val | 0%-0.01%-0% | rs377219791 | Spinal ALS-laboratory supported | P015 | [24,25] | |
| VCP | 5 | c.277C>T | p.Arg93Cys | 0%-0%-0% | Spinal ALS, no FTD, no Paget | P072 | [26,27] | ||
| VCP | 5 | c.463C>T | p.Arg155Cys | 0%-0%-0% | rs121909330 | (AR) IGHMBP2: c.2911_2912delAG (p.Arg971GlufsTer4) het [rs572973851; rs724159994, MAF *: 0%-0.82%-0.02%] (Class5) | Spinal ALS, no FTD, no Paget | P008 | [28,29] |
| SQSTM1 | 4 | c.695C>T | p.Pro232Leu | 0%-0%-0% | rs757778292 | (Suscep.) DAO: c.627G>A (p.Trp209Ter) het [rs766258671, MAF*: 0%-0%-0% ] (Suscep.) DCTN1: c.652G>A(p.Glu218Lys) het [MAF *: 0%-0%-0%] |
Bulbar ALS, onset 43 years | P002 | |
| SQSTM1 | 4 | c.301 + 4delA | p.? HSF: Alteration of the WT donor site, most probably affecting splicing. | 0%-0%-0% | (AR) IGHMBP2: c.2176G>A (p.Val726Met) het [rs143986510, MAF *: 0.02%-0.08%-0.04%] (Class3) | ALS | P103 | ||
| FIG4 |
5
4 |
c.122T>C c.1667C>T |
p.Ile41Thr p.Thr556Ile |
0.08%-0.11%-0.1% 0%-0%-0% |
rs121908287 |
Juvenile ALS with predominant upper motor neuron involvement | P100 | [30] | |
| SETX | 4 | c.2750T>C | p.Met917Thr | 0%-0.01%-0.01% | rs376022544 | ALS | P022 | [5] | |
| GARS1 | 4 | c.1955G>A | p.Gly652Glu | 0%-0%-0% | rs747080824 | ALS Pseudo-polyneuritic type |
P073 |
* MAF (minor allele frequency) % in 1000Genomes-Go-ESP-ExAC. Het: heterozygous; HSF: Human Splicing Finder; (Suscep.): variants in ALS susceptibility genes; (AR): variants in autosomal recessive genes.