Overview of pathogenic (P) and likely-pathogenic (LP) genetic variants, and candidate disease-causing variants (variants of unknown significance [VUS]) in the complete study cohort
| Participant ID | ERN | Cohort | Classification | Gene symbol (transcript) | Variant type | Inheritance | HGVS | gnomAD allele frequency | Orthogonal validation |
|---|---|---|---|---|---|---|---|---|---|
| P0185637 | ITHACA | Unsolvables | P | TUBA1A (NM_006009.4) | SNV | De novo AD | Chr12:g.49185725C > T, c.641G > A, p.(Arg214His) | Absent | – |
| P0695060 | EURO-NMD | Unsolved | P | DMD, NHS (NM_004006.3, NM_001291867.2) | SV (inversion) | XLR;XLD | ChrX:g.17398320_32130845inv | Absent | Sanger |
| P0078963 | EURO-NMD | Unsolved | P | DMD (NM_004006.3) | SV (inversion) | XLR | ChrX:g.23308848_32004110inv | Absent | OGM |
| P0016368 | RND | Unsolved | P | NOP56 (NM_006392.4) | STR | AD | Chr20:g.2652734_2652756GGCCTG[1200] | Absent | RNA-seq |
| P0018996 | RND | Unsolved | P | NOP56 (NM_006392.4) | STR | AD | Chr20:g.2652734_2652756GGCCTG[34] | Absent | RNA-seq |
| P0016356 | RND | Unsolved | P | DAB1 (NM_001365792.1) | STR | AD | Chr1:g.57367044_57367118AAAAT[29]GAAAT[117]AAAAT[615] | Absent | – |
| P0019022 | RND | Unsolved | P | RFC1 (NM_002913.5) | STR | AR | Chr4:g.39348427_39348476delinsAAGGG[1181]; Chr4:g.39348427_39348476delinsAAGGG[271] | Absent | RNA-seq |
| P0008178 | EURO-NMD | Unsolved | P | DMD (NM_004006.3) | SNV (deep intronic) | XLR | ChrX:g.33174335C > T, c.31 + 36947G > A | Absent | Sanger |
| P0016160 | RND | Unsolved | LP | SPAST (NM_041946.4) | SNV (intronic) | AD | Chr2:g.32115840G > A, c.1004 + 5G > A, p.(spl) | 6.24 × 10−4 | ES, exon-skipping, Sanger |
| P0631224 | RND | Unsolved | P; P | TTN (NM_001267550.2) | SNV | AR, maternally inherited, de novo on paternal allele | Chr2:g.178530761dup, c.105854dup, p.(Pro35286Thrfs*13); Chr2:g.178640613del, c.40652del, p.(Pro13551Glnfs*47) | Absent; Absent | SRS |
| P0657753 | EURO-NMD | Unsolved | LP | MYOT (NM_006790.3) | SV (tandem duplication) | AD | Chr5:g.137832296_137897203dup | Absent | SRS |
| P0011781 | RND | Unsolved | LP | REEP1 (NM_001371279.1) | SV (deletion) | AD | Chr2:g.86232216_86233399del, c.418-597_595 + 409del, p.(Gly140Cysfs*18) | Absent | PCR + LRS |
| P0237528 | EURO-NMD | Unsolved | VUS | REEP1 (NM_001371279.1) | SNV (deep intronic) | AD | Chr2:g.86327804T > C, c.32 + 9675A > G | 6.57 × 10−6 | – |
| P0936700 | EURO-NMD | Unsolved | VUS | FGF13, MCF2, and F9 (NM_004114.5, NM_001171876.2, NM_000133.4) | SV (duplication) | De novo AD/XLR | ChrX:g.139164887_139679311dup | Absent | PCR + LRS + cDNA + RNA-seq |
| P0021581 | EURO-NMD | Unsolved | VUS | PSMA3 (NM_002788.4) | SV (deletion) | De novo AD | Chr14:g.58268649_58283944del | Absent | PCR + Sanger |
| P0537031 | ITHACA | Unsolved | VUS | CPE, TLL1, NEK1, CLCN3, … | SV (5 Mb duplication) | N/A | Chr4:g.165447976_170473344dup | Absent | Array CGH, ES |
| P0016165 | RND | Unsolved | VUS | ARMC9, NCL | SV (300 kb duplication) | AD | Chr2:g.231348004_231684006dup | Absent | – |
[i] Allele frequency databases used: gnomAD v.4.1.0 (SNVs), gnomAD SVs v.4.1.0 (SVs), and gnomAD v.3.1.2 (STRs).