Table 1.
Molecular findings of the presently reported series of individuals with RAD21 variants
| PID | Reference | Source | CdLS scorea | Exon/intron | Nucleotide change | Predicted amino acid change | Type | Inheritance |
|---|---|---|---|---|---|---|---|---|
| Cohort A—sufficient clinical data | ||||||||
| F1 | Martinez 2017 | Updated | 9 | Exon 2 | c.68G > A | p.(Trp23*) | Nonsense | De novo |
| F2 | Clinvar | New | ≥ 7 | Exon 2 | c.194G > A | p.(Arg65Gln) | Missenseb | |
| F3a | Ansari 2014 P1 | Updated | ≥ 10 | Intron 3 | c.274 + 1G > A | Splice site | Familial (paternal) | |
| F4 | Minor 2014 P2 | Updated | 12 | Exon 6 | c.592_593dupAG | p.(Ser198Argfs*6) | Frameshift | |
| F5 | Unpublished | New | 9 | Exon 6 | c.617_620del | p.(Ile206Thrfs*3) | Frameshift | De novo |
| F6a | Boyle 2017 IV.16 | Updated | 12 | Exon 7 | c.704delG | p.(Ser235Ilefs*19) | Frameshift | Familial (maternal) |
| F6b | Boyle 2017 III.1 | Updated | 10 | Exon 7 | c.704delG | p.(Ser235Ilefs*19) | Frameshift | Familial (parents not tested) |
| F6c | Boyle 2017 III.2 | Updated | 9 | Exon 7 | c.704delG | p.(Ser235Ilefs*19) | Frameshift | Familial (parents not tested) |
| F6d | Boyle 2017 III.5 | Updated | 9 | Exon 7 | c.704delG | p.(Ser235Ilefs*19) | Frameshift | Familial (parents not tested) |
| F6e | Unpublished | New | 12 | Exon 7 | c.704delG | p.(Ser235Ilefs*19) | Frameshift | Familial (maternal) |
| F7 | Dorval 2019 | Original data | ≥ 11 | Exon 9 | c.943_946del | p.(Glu315Glnfs*9) | Frameshift | De novo |
| F8 | Deardorff 2012 P5 | Original data | ≥ 10 | Exon 9 | c.1127C > G | p.(Pro376Arg) | Missenseb | De novo |
| F9 | Kruszka 2019 P14 | Updated | 13 | Exon 10 | c.1217_1224del | p.(Lys406Argfs*4) | Frameshift | De novo |
| F10 | Unpublished | New | 10 | Exon 11 | c.1382C > T | p.(Thr461Ile) | Missense | Familial (paternal) |
| F11a | Minor 2014 P1 | Updated | 8 | Exon 13 | c.1621-388_1704 + 193del | p.(Asp541_Gln568del) | Inframe deletion | Familial (maternal) |
| F11b | Minor 2014 mother P1 | Updated | ≥ 5 | Exon 13 | c.1621-388_1704 + 193del | p.(Asp541_Gln568del) | 665 bp inframe deletion | |
| F12 | Unpublished | New | 13 | Exon 13 | c.1635del | p.(Gly547Alafs*65) | Frameshift | De novo |
| F13 | Deardorff 2012, P6 | Orginal data | ≥ 12 | Exon 14 | c.1753T > C | p.(Cys585Arg) | Missenseb | De novo |
| F14a | Unpublished | New | 12 | Exon 14 | c.1753T > C | p.(Cys585Arg) | Missenseb | Familial (parents not tested) |
| F14b | Unpublished | New | ≥ 10 | Exon 14 | c.1753T > C | p.(Cys585Arg) | Missense | Familial (parents not tested) |
| F15 | Unpublished | New | ≥ 12 | Exon 14 | c.1756C > T | p.(Arg586*) | Nonsense | |
| F16a | Unpublished | New | 10 | Exon 14 | c.1756C > T | p.(Arg586*) | Nonsense | Familial (paternal) |
| F16b | Father, unpublished | New | ≥ 10 | Exon 14 | c.1756C > T | p.(Arg586*) | Nonsense | |
| F17 | Gudmunsson 2019 | Updated | 8 | Exon 14 | c.1774_1776del | p.(Gln592del) | Inframe deletionb | De novo |
| F18 | Unpublished | New | 9 | Exon 14 | c.1800_1802del | p.(Phe600del) | Inframe deletionb | |
| F19 | Deardorff 2012 P4 | Original data | ≥ 12 | Whole gene | arr[hg19] 8q23.3q24.11(116880827–118875305)x1 | 2 Mb deletion | ||
| F20 | Unpublished | New | ≥ 12 | Whole gene | arr[hg19] 8q23.3q24.11(116915114–119171074)x1 | 2.3 Mb deletion | De novo | |
| F21 | Deardorff 2012 P2, McBrein 2008 | Original data | ≥ 12 | Whole gene | arr[hg19] 8q23.3q24.12(117571728–119260904)x1 | 1.7 Mb deletion | De novo | |
| F22 | Unpublished | New | 12 | Exons 1–9 | arr[hg19] 8q24.11(117866471–117893495)x1 | 27 kb deletion | ||
| Cohort B—insufficient clinical data | ||||||||
| F3b | Ansari 2014 | Updated | Intron 3 | c.274 + 1G > A | n/a | Splice site | ||
| F23 | Decipher 271431 | New | Exon 2 | c.16T > G | p.(Phe6Val) | Missense | De novo | |
| F24 | Unpublished | New | Exon 2 | c.85delinsCCT | p.(Lys29Profs*10) | Frameshift | ||
| F25a | Decipher 272901 | New | Exon 9 | c.951del | p.(Ala318Profs*7) | Frameshift | Familial (paternal) | |
| F25b | Decipher 272901 father | New | Exon 9 | c.951del | p.(Ala318Profs*7) | Frameshift | ||
| F26 | Decipher 275402 | New | Exon 9 | c.1033T > C | p.(Ser345Pro) | Missenseb | De novo | |
| F27a | Yuan 2018 P2 | Updated | Intron 10 | c.1161 + 1G > A | Splice site | Familial (maternal) | ||
| F27b | Yuan 2018 mother P2 | Updated | Intron 10 | c.1161 + 1G > A | Splice site | |||
| F28a | Kruszka 2019 P12/Yuan 2019 P1 | Updated | Exon 12 | c.1550dupC | p.(Glu518Argfs*19) | Frameshift | Familial (paternal) | |
| F28b | Kruszka 2019 P12 father/Yuan 2019 P1 father | Updated | Exon 12 | c.1550dupC | p.(Glu518Argfs*19) | Frameshift | ||
| F29 | Lee 2014 P76 | Original data | Exon 14 | c.1808T > C | p.(Leu603Pro) | Missenseb | De novo | |
| F30a | Bonora 2015 IV.9 | Updated | Exon 14 | c.[1864G > A];[1864G > A] | p.(Ala622Thr) | Missenseb | Familial (both parents) | |
| F30b | Bonora 2015 IV.10 | Updated | Exon 14 | c.[1864G > A];[1864G > A] | p.(Ala622Thr) | Missenseb | Familial (both parents) | |
| F30c | Bonora 2015 IV.11 | Updated | Exon 14 | c.[1864G > A];[1864G > A] | p.(Ala622Thr) | Missenseb | Familial (both parents) | |
| F30d | Unpublished | New | Exon 14 | c.[1864G > A] | p.(Ala622Thr) | Missenseb | Familial (nos) | |
| F30e | Unpublished | New | Exon 14 | c.[1864G > A] | p.(Ala622Thr) | Missenseb | Familial (nos) | |
| F30f | Unpublished | New | Exon 14 | c.[1864G > A] | p.(Ala622Thr) | Missenseb | Familial (nos) | |
| F31 | ClinVar | New | Whole gene | arr[hg19] 8q23.3-24.11(116902507–118942698)x1 | 2 Mb deletion; includes several genes | |||
| F32 | ClinVar | New | Whole gene | arr[hg19] 8q23.3-24.11(117509968–118391406)x1 | 880 kb deletion; includes several genes | |||
| F33 | ClinVar | New | Whole gene | arr[hg19] 8q24.11(117714768–119072307)x1 | 1.4 Mb deletion; includes several genes | |||
Cohort A: detailed clinical data available, including information on all cardinal CdLS features; cohort B: insufficient clinical data available
F family number, P patient number in the respective publication, nos not otherwise specified
aBased on (Kline et al. 2018); ≥ defines at least (minor criteria missing). Score < 4 is insufficient to indicate molecular testing for CdLS; score 4–8 indicates molecular testing for CdLS indicated; score 9–10 indicates non-classic CdLS; score 11 or higher indicates classic CdLS
bVariants investigated with protein modelling