Table 2.
List of causative genetic variants identified in 28 Austrian patients with CMS
| Patient ID | Gene (transcript) | Variant [zygosity] |
ACMG criteria fulfilled | ACMG classification |
|---|---|---|---|---|
| 1 | RAPSN (NM_005055.5) |
c.264C>A, p.(Asn88Lys) [homozygous] |
PS1, PS3, PM1, PM2, PM3, PP3 | Pathogenic |
| 2 |
CHRNE |
c.1327del, p.(Glu443Lysfs*64) [homozygous] |
PVS1, PM2, PM3, PP3 | Pathogenic |
| 3 | CHAT (NM_020549.5) |
c.1669G>A, p.(Ala557Thr) [heterozygous] |
PS1, PM2, PM3, PP3 | Likely pathogenic |
|
c.1267G>A, p.(Asp423Asn) [heterozygous] |
PM1, PM2, PM3, PP3 | Likely pathogenic | ||
| 4 | DOK7 (NM_173660.5) |
c.1388_1446del, p.(Glu463Glyfs*36) [heterozygous] |
PVS1, PM2, PM3, PP3 | Pathogenic |
|
c.1124_1127dup, p.(Ala378Serfs*30) [heterozygous] |
PVS1, PM2, PM3, PP3 | Pathogenic | ||
| 5 |
CHRNE |
c.1327del, p.(Glu443Lysfs*64) [homozygous] |
PVS1, PM2, PM3, PP3 | Pathogenic |
| 6 |
CHRNE |
c.1327del, p.(Glu443Lysfs*64) [homozygous] |
PVS1, PM2, PM3, PP3 | Pathogenic |
| 7 | GMPPB (NM_021971.4) |
c.79G>C, p.(Asp27His) [heterozygous] |
PS1, PM1, PM2, PM3, PP3 | Likely pathogenic |
|
c.848G>C, p.(Gly283Ala) [heterozygous] |
PM1, PM2, PM3, PP3 | Likely pathogenic | ||
| 8 | DOK7 (NM_173660.5) |
c.439dup, p.(Ala147Glyfs*10) [heterozygous] |
PVS1, PM2, PM3, PP3 | Pathogenic |
|
c.1124_1127dup, p.(Ala378Serfs*30) [heterozygous] |
PVS1, PM2, PM3, PP3 | Pathogenic | ||
| 9 |
CHRNE |
c.1327del, p.(Glu443Lysfs*64) [homozygous] |
PVS1, PM2, PM3, PP3 | Pathogenic |
| 10 |
CHRNE |
c.1327del, p.(Glu443Lysfs*64) [homozygous] |
PVS1, PM2, PM3, PP3 | Pathogenic |
| 11 | AGRN (NM_198576.4) |
c.3419T>C, p.(Leu1140Pro) [heterozygous] |
PM1, PM2, PM3 | Likely pathogenic |
|
chr1.hg19: g.896373_975646del [heterozygous] |
PVS1, PM2, PM3 | Pathogenic | ||
| 12 | COLQ (NM_005677.3) |
c.965T>G, p.(Val322Gly) [heterozygous] |
PM1, PM2, PP3, PP4 | Likely pathogenic |
|
c.1026C>G, p.(Asp342Glu) [heterozygous] |
PM1, PM2, PP3, PP4 | Likely pathogenic | ||
| 13 |
CHRNE |
c.1327del, p.(Glu443Lysfs*64) [homozygous] |
PVS1, PM2, PM3, PP3 | Pathogenic |
| 14 |
CHRNE |
c.1327del, p.(Glu443Lysfs*64) [homozygous] |
PVS1, PM2, PM3, PP3 | Pathogenic |
| 15 | DOK7 (NM_173660.5) |
c.1124_1127dup, p.(Ala378Serfs*30) [heterozygous] |
PVS1, PM2, PM3, PP3 | Pathogenic |
|
c.472C>T, p.(Arg158Trp) [heterozygous] |
PM1, PM2, PM3 | Likely pathogenic | ||
| 16 |
CHRNE |
c.1327del, p.(Glu443Lysfs*64) [homozygous] |
PVS1, PM2, PM3, PP3 | Pathogenic |
| 17 | DOK7 (NM_173660.5) |
c.1124_1127dup, p.(Ala378Serfs*30) [heterozygous] |
PVS1, PM2, PM3, PP3 | Pathogenic |
|
c.1378dup, p.(Gln460Profs*59) [heterozygous] |
PVS1, PM2, PM3, PP3 | Pathogenic | ||
| 18 | GMPPB (NM_021971.4) |
c.79G>C, p.(Asp27His) [heterozygous] |
PS1, PM1, PM2, PM3, PP3 | Likely pathogenic |
|
c.860G>A, p.(Arg287Gln) [heterozygous] |
PS1, PM1, PM2, PM3 | Pathogenic | ||
| 19 |
CHRNE |
c.1327del, p.(Glu443Lysfs*64) [homozygous] |
PVS1, PM2, PM3, PP3 | Pathogenic |
| 20 | MUSK (NM_005592.4) |
c.1744G>A, p.(Gly582Arg) [heterozygous] |
PM1, PM2, PM3, PP3, PP4 | Likely pathogenic |
|
c.698G>A, p.(Cys233Tyr) [heterozygous] |
PM1, PM2, PM3, PP3, PP4 | Likely pathogenic | ||
| 21 |
CHRNE |
c.1326+1G>A, p? [homozygous] |
PVS1, PM2, PM3, PP1, PP3 | Pathogenic |
| 22 |
CHRNE |
c.1326+1G>A, p? [homozygous] |
PVS1, PM2, PM3, PP1, PP3 | Pathogenic |
| 23 | COLQ (NM_005677.4) |
c.943C>T, p.(Arg315*) [homozygous] |
PVS1, PM2, PM3, PP3 | Pathogenic |
| 24 | COL13A1 (NM_001368882.1) |
c.715-1G>A, p? [homozygous] |
PVS1, PM2, PM3, PP3 | Pathogenic |
| 25 | RAPSN (NM_005055.5) |
c.193-15C>A, p? [heterozygous] |
PS3, PM2, PM3, PP1, PP3 | Likely pathogenic |
|
c.264C>A, p.(Asn88Lys) [heterozygous] |
PS1, PS3, PM1, PM2, PM3, PP1, PP3 | Pathogenic | ||
| 26 | RAPSN (NM_005055.5) |
c.193-15C>A, p? [heterozygous] |
PS3, PM2, PM3, PP1, PP3 | Likely pathogenic |
|
c.264C>A, p.(Asn88Lys) [heterozygous] |
PS1, PS3, PM1, PM2, PM3, PP1, PP3 | Pathogenic | ||
| 27 |
CHRNE |
c.872C>T, p.(Ala291Val) [heterozygous] |
PM1, PM2, PM3, PP1, PP3 | Likely pathogenic |
|
c.103T>C, p.(Tyr35His) [heterozygous] |
PM1, PM2, PM3, PP1, PP3 | Likely pathogenic | ||
| 28 |
CHRNE |
c.872C>T, p.(Ala291Val) [heterozygous] |
PM1, PM2, PM3, PP1, PP3 | Likely pathogenic |
|
c.103T>C, p.(Tyr35His) [heterozygous] |
PM1, PM2, PM3, PP1, PP3 | Likely pathogenic |
ACMG American College of Medical Genetics and Genomics; PM pathogenic moderate; PP pathogenic supporting; PS pathogenic strong; PVS pathogenic very strong